Symptoms of C.F.S. are similar to those of most common viral infections (muscle aches, headache, and fatigue), often developing within a few hours or days and lasting for 6 months or more.

Main symptoms:

• fatigue or tiredness, never experienced to this extent before (new onset), lasting at least 6 months and not relieved by bed rest
• fatigue that is severe enough to restrict activity (serious fatigue develops with less than one-half of the exertion compared to before the illness)

Other symptoms:

• fatigue lasting more than 24 hours that develops after an amount of exercise that would normally be easily tolerated
• mild fever (low-grade: 101 degrees F or less)
• sore throat
• lymph node tenderness in the neck or armpit (axilla)
• muscle weakness, all over or multiple locations, not explained by any known disorder
• muscle aches (myalgias)
• sleep disturbances: sleeping too much (hypersomnia) or difficulty falling asleep or remaining asleep (insomnia)
• headaches, different from previous headaches in quality, severity, or pattern
• joint pain, often moving from joint to joint (migratory arthralgias), without joint swelling or redness
• unusual nervous system symptoms, such as:
  • increased sensitivity of eyes to light (photophobia)
  • forgetfulness
  • irritability
  • confusion
  • thinking seems "fuzzy" or "foggy"
  • difficulty concentrating
  • depression

Physical examination may confirm the fever, lymph node tenderness, lymph node swelling, or other symptoms. The throat may appear red without drainage or pus.

The health care provider can presume a diagnosis of chronic fatigue syndrome (or C.F.S.) only after ruling out all other known possible causes of fatigue, such as:

• infections.
• immune or autoimmune disorders.
• tumors.
• muscle or nerve diseases (such as multiple sclerosis).
• endocrine diseases (such as hypothyroidism).
• psychiatric or psychological illnesses, particularly depression. Since Chronic Fatigue Syndrome itself may be associated with depression, a diagnosis of depression does not rule out CFS but fatigue related to depression alone must be ruled out for CFS to be diagnosed.
• drug dependence.
• other illnesses (such as heart, kidney, liver diseases).

A diagnosis of C.F.S. must include:

• extreme, prolonged fatigue
• absence of other causes of chronic fatigue (excluding depression)
  • at least 6 of the other symptoms listed plus two confirming physical examination findings (or)
  • at least 8 of the other symptoms listed

There are no specific tests to confirm the diagnosis of C.F.S., though a variety of tests are usually done to exclude other possible causes of the symptoms.

There are some "typical" findings on tests that, while not specific enough to diagnose C.F.S., are seen consistently in people who are eventually diagnosed with the disorder. These include:

• higher levels of specific white blood cells (CD4 T cells) compared to other types of white blood cells (CD8 T cells)
• brain MRI shows swelling in the brain or destruction of part of the nerve cells (demyelination)
• specific white blood cells (lymphocytes) frequently contain active forms of herpes virus-6