Chronic Fatigue Syndrome

Chronic Fatigue Syndrome (myalgic encephalomyelitis, ME/CFS) is a long-lasting illness marked by post-exertional malaise (PEM)—a crash after physical or mental effort—plus unrefreshing sleepcognitive difficulties, and often orthostatic intolerance (worse symptoms upright). There is no single blood test that diagnoses ME/CFS. Diagnosis is clinical and based on symptom patterns and duration, while lab testing helps rule out other conditions, identify contributors, and monitor overall health.

A proactive plan usually begins with core fatigue labs (CBC, CMP, TSH/free T4, iron panel with ferritin, vitamin B12 ± MMA, folate, vitamin D, A1c/glucose, CRP/ESR). Depending on your history, your clinician may add celiac screeningautoimmune screensmorning cortisol ± ACTH, and targeted infectious disease tests. Results guide screeningdiagnostic triage, and monitoring, but they do not replace clinician evaluation, autonomic testing for orthostatic intolerance, sleep assessment, or emergency care.

Signs, Symptoms & Related Situations

  • Energy & exertion: profound fatigue not relieved by rest; PEM hours to days after activity

  • Cognitive (“brain fog”): trouble focusing, slowed thinking, word-finding issues

  • Sleep: unrefreshing sleep, reversed schedule, insomnia or hypersomnia

  • Autonomic/orthostatic: lightheadedness on standing, palpitations, “hangover” feeling after being upright; suspect POTS/orthostatic intolerance

  • Pain & sensory: muscle/joint pain, headaches, sensitivity to light/sound

  • Immune/infectious context: post-viral onset, frequent sore throats, tender lymph nodes

  • Overlapping conditions: thyroid disorders, anemia or iron deficiency, diabetes/prediabetes, celiac disease, liver/kidney disease, depression/anxiety, sleep apnea, medication effects, fibromyalgia

  • Seek urgent care now: chest pain, severe shortness of breath, fainting, confusion, black/bloody stools, high fever, or rapidly worsening neurologic symptoms

Symptoms and risks must be evaluated by a qualified clinician.

Why These Tests Matter

What testing can do

  • Rule out common mimics of chronic fatigue (thyroid imbalance, anemia/iron deficiency, B12/folate deficiency, diabetes, celiac disease, liver/kidney dysfunction)

  • Characterize inflammation or metabolic stress (CRP/ESR, A1c, CMP) and establish baselines to monitor over time

  • Support targeted follow-up for suspected orthostatic, autoimmune, endocrine, or nutritional contributors

What testing cannot do

  • Diagnose ME/CFS directly—no stand-alone lab confirms it

  • Measure PEM or autonomic intolerance; those require clinical assessment and, when indicated, autonomic/tilt testing

  • Replace sleep evaluation, mental-health assessment, or clinician judgment about next steps

What These Tests Measure (at a glance)

  • CBC (Complete Blood Count): anemia, infection clues

  • Iron panel with ferritin (Iron, TIBC, Transferrin Saturation): detects iron deficiency and iron distribution

  • Vitamin B12 with MMA ± Homocysteine; Folate: identifies functional B12/folate deficits that affect nerves and energy

  • 25-Hydroxy Vitamin D: bone/muscle and immune context

  • TSH ± Free T4: rules out hypo-/hyperthyroidism

  • CMP: electrolytes, kidney/liver function, glucose; albumin/protein for nutrition context

  • A1c ± fasting glucose: screens for diabetes/prediabetes

  • CRP/ESR: markers of systemic inflammation (steady-state)

  • Morning Cortisol ± ACTH (history-guided): screens low cortisol patterns; consider free cortisol tests when high cortisol is suspected

  • Celiac screen (tTG-IgA with total IgA): evaluates gluten-related autoimmunity in persistent GI or malabsorption clues

  • Autoimmune screens (selected): ANA (± reflex patterns), ± RF/CCP or thyroid antibodies when indicated

  • Targeted infectious disease tests: clinician-directed (timed to symptoms/exposure; routine broad panels are not recommended without indications)

Quick Build Guide

Goal / Scenario Start with Add if needed
Baseline fatigue workup CBC • CMP • TSH/free T4 • Ferritin/Iron/TIBC • B12 ± MMA • Folate • 25-OH Vitamin D • A1c • CRP/ESR Magnesium • Vitamin C • Zinc
Post-viral onset Baseline panel (above) Targeted serologies only if clinically indicated
Orthostatic symptoms (lightheaded, palpitations upright) Baseline panel Electrolytes review • Morning cortisol; clinical autonomic testing is separate
GI symptoms/weight loss/malabsorption Baseline panel Celiac tTG-IgA + total IgA • Iron studies • B12/MMA • Vitamin D
Pain, stiffness, rash, dry eyes/mouth Baseline panel ANA (± reflex) • RF/CCP (as guided)
Sleep concerns/snoring ≥ loud or witnessed apneas Baseline panel Sleep evaluation (out of scope for blood testing)
Athlete/overtraining pattern CBC • CMP • Ferritin • TSH CRP • Vitamin D • CK

How the Testing Process Works

  1. Choose your starting bundle: most people begin with the baseline fatigue panel above.

  2. Prepare for accuracy: fasting is not required unless your order includes fasting glucose/lipids. Avoid high-dose biotin for 24–48 hours if advised.

  3. Provide samples: standard blood draw; celiac testing requires serum; cortisol timing is morning unless otherwise directed.

  4. Get secure results: most post within a few days.

  5. Review and plan: discuss results with your clinician to confirm exclusions, consider autonomic/sleep assessments, and set a monitoring cadence.

Interpreting Results (General Guidance)

  • Low ferritin and low transferrin saturation → iron deficiency pattern; correlate with CBC and history

  • Low B12 or high MMA → functional B12 deficiency; check for neuropathy or cognitive changes

  • Abnormal TSH/free T4 → thyroid imbalance may explain fatigue and temperature intolerance

  • Elevated CRP/ESR → systemic inflammation; interpret with symptoms/exam

  • Normal labs do not rule out ME/CFS—diagnosis relies on symptom criteria and clinical evaluation
    Trends over time matter more than a single value; always review results with a qualified healthcare professional.

Choosing Panels vs. Individual Tests

  • Core ME/CFS workup: CBC • CMP • TSH/free T4 • Ferritin/Iron/TIBC • B12 ± MMA • Folate • 25-OH Vitamin D • A1c • CRP/ESR

  • Add-ons by history: Celiac screen (tTG-IgA + total IgA) • Morning Cortisol ± ACTH • ANA (± reflex) • RF/CCP • Thyroid antibodies

  • Nutrient depth (as needed): Zinc • Magnesium (± RBC) • Vitamin C
    Use bundled panels for efficient screening; add targeted markers to answer specific questions and monitor progress.

FAQs

Is there a blood test that proves ME/CFS?
No. ME/CFS is a clinical diagnosis. Labs help exclude other causes and track overall health.

Which tests should I start with?
baseline fatigue panel (CBC, CMP, thyroid, iron/ferritin, B12 ± MMA, folate, vitamin D, A1c, CRP/ESR) is a practical first step.

Do I need to fast?
Usually no. Fast only if fasting glucose or lipids are ordered.

Should I test for infections like EBV or Lyme right away?
Not routinely. Targeted testing is best when symptoms, exposure, or clinician guidance indicate.

Can cortisol testing diagnose ME/CFS?
No. Cortisol labs can reveal other endocrine issues, but they do not diagnose ME/CFS.

My labs are normal—now what?
ME/CFS can exist with normal labs. Talk with your clinician about symptom criteriaactivity pacing strategies, and evaluation of orthostatic intolerance or sleep issues.

How often should I re-test?
Many people recheck every 3–6 months to monitor trends or after clinical/lifestyle changes—follow your clinician’s plan.

Related Categories & Key Tests

  • Stress & Fatigue Tests Hub

  • All Stress & Fatigue Tests • Adrenal Stress Tests • Thyroid Tests • Anemia & Blood Count • Nutrition Tests • Inflammation Tests • Sleep & Wellness Panels

  • Key Tests: CBC • CMP • TSH • Free T4 • Ferritin • Iron/TIBC • Transferrin Saturation • Vitamin B12 • MMA • Folate • 25-OH Vitamin D • A1c • Fasting Glucose • CRP • ESR • Morning Cortisol • ACTH • Celiac tTG-IgA + Total IgA • ANA (± reflex) • RF • CCP

References

  • Centers for Disease Control and Prevention — ME/CFS overview and clinical guidance.
  • National Academy of Medicine (formerly IOM) — Beyond Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Redefining an Illness.
  • NICE Guideline (UK) — Myalgic encephalomyelitis (or encephalopathy)/chronic fatigue syndrome: diagnosis and management.
  • AHRQ Systematic Review — Diagnosis and Treatment of Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.
  • American College of Physicians — High-value care guidance on evaluation of chronic fatigue.
  • Clinical reviews on orthostatic intolerance/POTS in ME/CFS and laboratory exclusion of common mimics.

Available Tests & Panels

Your Chronic Fatigue Syndrome (ME/CFS) Tests menu is pre-populated in the Ulta Lab Tests system. Start with a core fatigue panel to rule out common mimics, then use filters to add celiac screeningautoimmune screens, or cortisol/ACTH based on your history. Follow collection instructions and review results with your clinician to align labs with autonomic or sleep evaluations and set a monitoring plan.

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The Zinc Test measures zinc levels in blood to evaluate nutritional status and overall health. Zinc is essential for immune function, wound healing, growth, taste, and reproductive health. Abnormal levels may cause fatigue, hair loss, delayed healing, or increased infection risk. Doctors use this test to detect zinc deficiency or excess, monitor supplementation, and guide treatment for conditions linked to immune, metabolic, or endocrine imbalance.

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The Zinc Protoporphyrin (ZPP) Test measures ZPP levels in red blood cells to detect iron deficiency and lead exposure. When iron is low or lead interferes with hemoglobin production, ZPP accumulates, making it a sensitive early marker. Doctors use this test to screen for iron-deficiency anemia, monitor occupational lead exposure, and evaluate unexplained anemia, helping guide diagnosis, prevention, and treatment strategies.

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The Methylation Essentials Panel provides a comprehensive baseline evaluation of core laboratory markers involved in the body’s methylation process. Methylation is a fundamental biochemical pathway that supports nutrient metabolism, cardiovascular wellness, energy production, and cellular maintenance.

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The Advanced Methylation Precision Panel is Ulta Lab Tests’ most comprehensive evaluation of methylation-related health. This panel organizes laboratory testing across core methylation pathways, integrating nutrient status, functional biomarkers, genetic factors, inflammation, oxidative stress, and metabolic context.

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The Methylation Pathway Optimization Panel provides a comprehensive evaluation of the key nutrients, functional biomarkers, and genetic factors that influence methylation efficiency. Methylation is a critical biochemical process involved in cardiovascular wellness, energy production, cognitive function, and cellular maintenance.

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Panel Contains Test: Comprehensive Methylation Test, Advanced Epigenetic Health Panel, Methylation, Inflammation & Oxidative Stress Panel, Precision Nutrient & Gene Interaction Panel, Epigenetic Regulation & Methylation Panel, Cellular Repair

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Extreme fatigue that is ongoing and cannot be explained by a medical condition or has no other scientifically proven cause is called Chronic Fatigue Syndrome or CFS. Chronic Fatigue Syndrome can be detrimental to a person’s ability to perform and complete even the most basic daily or routine tasks and activities.

Even though a person is continuously fatigued, they have trouble sleeping and often wake to feel as if they have not slept at all.

Other symptoms that they may experience include:

  • Recurrent headaches
  • Pain in the joints and muscles
  • Frequent sore throat
  • Problems with memory, focus, and concentration

Not every person may experience all these symptoms and may be affected to varying degrees, which may change from day to day. In extreme cases, CFS can last for an extended period exceeding six months. A person may be able to function almost normally on days when the symptoms are mild but on bad days, may not be able to get out of bed at all. Resting and sleeping do not resolve chronic fatigue, and mental activity may increase the symptoms.

CFS can affect any person regardless of age, gender, ethnicity, or economic standing anywhere in the world. However, the disorder is estimated to be four times as prevalent in females than in males and in those between the ages of 40 and 50 years. The CDC (Centers for Disease Control and Prevention) has estimated that around 1 million people in the United States have CFS. However, only around 20% of these know that they have the disorder and have been formally diagnosed.

Currently, there is very little known about the cause of CFS. Although a single cause has not been identified, scientific research has revealed several different triggers that include the following:

  • Although no specific microbe has been attributed to the cause of CFS, viral infections like the Epstein Barr Virus may trigger the condition
  • Trauma, stress, or allergies that result in immune dysfunction may, in turn, trigger CFS
  • Malnourishment or nutritional deficiencies
  • Neurally mediated hypotension or extremely low blood pressure causing fainting may be a trigger
  • Disturbances in the hypothalamic-pituitary-adrenal (HPA) axis, which may result from inactivity, psychiatric comorbidity, extended stress, disturbances in sleep patterns, and medication
  • After studying familial CFS patterns, researchers believe that there may be a genetic component that would make certain people more predisposed to the disorder

Current research points to CFS being a group of disorders that all result in the same symptoms rather than a singular condition. However, more research is required for scientific confirmation.

A definitive group of onset symptoms has been identified by those who have been diagnosed with CFS. In other words, specific symptoms that they experienced during a time when they had the required energy to function and complete routine tasks. It has been concluded that around 75% of the time, CFS patients experience what appear to be flu-like symptoms. In other patients, CFS followed an extended or extreme period of mental or physical stress. The symptoms of CFS also develop slowly, resulting in a gradual decline in energy levels and overall wellbeing.

There are, however, several illnesses, diseases, and health conditions that may present with a similar set of symptoms and side effects but must be distinguished from CFS. These conditions are the underlying cause of chronic fatigue and may be short or long-term. Some diseases that may present with chronic fatigue but must exclude a diagnosis of CFS include:

  • Hypothyroidism or thyroid that is under-performing
  • Mononucleosis commonly called mono
  • Psychological disorders or mental health conditions
  • Eating disorders like anorexia or bulimia
  • Cancer and cancer treatments
  • Autoimmune diseases
  • Infection
  • Abuse or addiction to substances such as drugs and alcohol
  • Side effects or reactions to prescription medications
  • An inability to achieve enough uninterrupted sleep

Unfortunately, there is currently no single evaluation or test that can be used to diagnose CFS accurately. The signs and symptoms of the disorder are used as qualifying criteria to reach a diagnosis.

Signs And Symptoms Of CFS

On conjunction with a panel of international expert researchers, the CDC have established a definition for Chronic Fatigue Syndrome and a list of signs and symptoms that therefore define the disorder:

  • Severe chronic fatigue must last for a minimum period of 6 consecutive months or longer without any known medical conditions having been previously clinically diagnosed
  • The ability to perform basic or routine daily tasks must be severely affected

A minimum of four of the following eight symptoms must occur during the six-month period, either ongoing or on a recurring basis:

  • An inability to concentrate, shortened attention span, and impaired short-term memory
  • Frequent or persistent sore throat
  • Lymph nodes in the neck or armpits that are sore and tender
  • Pain in muscles
  • Multiple joint pain that is unaccompanied by inflammation (swelling) and/or redness
  • Unfamiliar headaches, more extreme or occurring in new patterns
  • Waking up feeling unrefreshed
  • Extreme fatigue that lasts more than 24 hours after mental or physical activity

The National Academy of Medicine Committee on Diagnostic Criteria for Myalgic Encephalomyelitis (Chronic Fatigue Syndrome) released additional diagnostic criteria in a report for CFS to improve on the existing criteria for diagnosis and care of those who are suffering from the health condition. Some of the criteria are similar or the same as those that have been outlined above. Additional criteria that medical practitioners can use to diagnose the ME or CFS accurately include:

  • Extreme fatigue must be new and be present for more than six months, defined by a specific beginning. It should not have been caused by excessive exercise and cannot be improved by resting. It must affect the ability to perform basic daily activities such as work, school personal hygiene to a certain degree.
  • It must negatively impact general wellbeing and present with a general feeling of malaise (illness), which is increased after expending energy

One of the following symptoms should also be present at least 50% of the time, and it must be determined how severe and how often they occur:

  • Cognitive Impairment resulting in an inability to concentrate for a period of time, a short attention span as well as problems with memory
  • Orthostatic Intolerance is feeling dizzy or light-headed or having heart palpitations when rising from a sitting or resting position that could result in faintness or fainting

The less common side effects and symptoms of CFS include:

  • Gastrointestinal conditions such as abdominal pain, bloating, loss of appetite, nausea, and/or vomiting
  • Sensitivity or an adverse reaction (allergic reaction) to certain foods, odors, sounds, medications, or chemicals
  • Night sweats or chills
  • Constant or consistent (chronic) coughing
  • Anxiety and/or depression
  • Frequent urination
  • Sensitivity to cold and heat
  • Lowered body temperature
  • Dry mouth and eyes
  • Earache
  • TMJ (Temporomandibular Joint) dysfunction or pain in the jaw
  • Mild fever
  • Stiff joints, particularly in the mornings
  • A sensation of numbness, tingling, or burning in the extremities (hands and feet) and the face
  • Shortness of breath

Tests For CFS

As there are currently no specific blood tests, imaging scans, or other means of an accurate diagnosis for chronic fatigue syndrome, diagnosis is one of exclusion. This means that all illnesses, disease, or other health conditions that may present with similar symptoms must be excluded before arriving at a diagnosis of CFS.

Diagnosis will, therefore, involve the following:

  • Detailed documentation of the medical history of a patient
  • A thorough medical examination
  • Performing cognitive function tests
  • Excluding any other conditions that may be causing or aggravating fatigue as well as providing treatment for those conditions that can be treated
  • Ensuring that the condition fulfills the criteria to meet the CDC definition and/or National Academy of Medicine criteria
  • Monitoring of a patient over a period of time to evaluate whether there may be any other underlying causes

Classification of idiopathic or unknown chronic fatigue will be made should the condition fail to meet the CDC definition or the National Academy of Medicine criteria or where the symptoms are not severe enough to warrant a diagnosis of CFS.

As there is currently no definitive test to diagnose CFS, laboratory testing is used to eliminate and provide treatment options for health conditions or disorders with similar symptoms. The CDC provides guidelines for the basic tests that should be performed, but these could be dependent on other symptoms as well as the health care practitioner managing the case.

Laboratory Tests For Exclusion Purposes

A Comprehensive Metabolic Panel (CMP) includes a variety of different tests to determine the health of organs and identify a range of health conditions such as kidney and liver disease.

A Complete Blood Count (CBC) evaluates blood disorders specifically to look for infection or anemia and other conditions.

C-reactive Protein or Erythrocyte Sedimentation rate, which acts as indicators of nonspecific inflammation in the body.

Thyroid Stimulating Hormone (TSH), including other types of thyroid testing for hypothyroidism.

Iron Studies to detect anemia or an iron deficiency.

Urinalysis to identify infections or other conditions.

Any additional tests that a medical practitioner deems necessary in identifying diseases or health conditions or excluding them as causes of the symptoms of CFS. These additional tests may include:

Antinuclear Bodies (ANA) to identify autoimmune disorders.

Lyme disease tests if the disease is suspected, and the geographical area gives cause for testing.

Rheumatoid Factor to detect Rheumatoid Arthritis.

HIV Antibody Test to identify or eliminate an HIV infection.

Cortisol Testineg to identify low concentrations of cortisol as well as adrenal gland function.