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 will diagnose chronic fatigue syndrome (CFS) only after ruling out all other known possible causes of fatigue, such as:

• Drug dependence
• Immune or autoimmune disorders
• Infections
• Muscle or nerve diseases (such as multiple sclerosis)
• Endocrine diseases (such as hypothyroidism)
• Other illnesses (such as heart, kidney, liver diseases)
• Psychiatric or psychological illnesses, particularly depression (since CFS 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)
• Tumors

A diagnosis of CFS must include:

• Absence of other causes of chronic fatigue (excluding depression)
• At least four of the other symptoms listed
• Extreme, prolonged fatigue

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

The following test results, while not specific enough to diagnose CFS, are seen consistently in people who are eventually diagnosed with the disorder:

• Brain MRI showing swelling in the brain or destruction of part of the nerve cells (demyelination)
• Higher levels of specific white blood cells (CD4 T cells) compared with other types of white blood cells (CD8 T cells)
• Specific white blood cells (lymphocytes) containing active forms of EBV or HHV-6

There is currently no cure for CFS. Instead, the symptoms are treated. Many people with CFS experience depression and other psychological problems that may improve with treatment.

Some of the proposed treatments include:

• Antiviral drugs (such as acyclovir)
• Drugs to fight yeast infections (such as nystatin)
• Medications to reduce pain, discomfort, and fever
• Medications to treat anxiety (antianxiety drugs)
• Medications to treat depression (antidepressant drugs)

Some medications can cause adverse reactions or side effects that are worse than the original symptoms of chronic fatigue syndrome.

Patients with CFS are encouraged to maintain active social lives. Mild physical exercise may also be helpful.