What Causes Chronic Fatigue Syndrome?

Patient Expert

By Karen Lee Richards, ChronicPainConnection Lead Expert

Currently, the cause of chronic fatigue syndrome (also called myalgic encephalopathy or ME/CFS) remains a mystery. While it frequently occurs following a cold, flu or viral infection, it can also begin during a time of severe physical or emotional stress. In some cases, however, it will develop gradually and have no clear starting point. Although research over the past two decades has revealed a number of very real, physical abnormalities, it has yet to yield a definitive cause for chronic fatigue syndrome.

Over the years, a number of theories have been proposed and studied. Some possible causes that have been looked at include:

  • Virus infection (for example, Epstein-Barr or human herpesvirus6)
  • Hormonal changes in the hypothalamus, pituitary or adrenal glands
  • Allergies
  • Mild, chronic low blood pressure
  • Low blood sugar (hypoglycemia)
  • Iron deficiency anemia

A number of studies have found immune system irregularities in chronic fatigue syndrome patients. A particularly promising area of immune system research is delving into the theory that ME/CFS patients have an overactive immune system. Imbalances in T-cells (white blood cells that act as infection fighters) have been reported in several studies. Abnormal T-cells cause the immune system to become persistently overactive and produce an excess of cytokines, an inflammatory substance that can damage the cells, producing fatigue, muscles aches and other ME/CFS symptoms. Two cytokines in particular, interleukin-6 and interleukin-1, are elevated in chronic fatigue syndrome patients. Although the cause of the overproduction is unknown, researchers agree that cytokine over-production plays an important role in ME/CFS and might eventually be used as a marker to identify the illness.

Many experts believe that chronic fatigue syndrome develops from a convergence of two or more factors. They theorize that one or more of these factors may interact with certain neurological or genetic abnormalities, triggering ME/CFS. Those factors may include:

  • Genetic factors
  • Brain abnormalities
  • A hyper-reactive immune system
  • Viral or other infectious agents
  • Psychiatric or emotional conditions

More info on the Causes of Chronic Fatigue Syndrome


"About CFIDS," The CFIDS Association of America, Inc., 2004

"Chronic Fatigue Syndrome," MayoClinic.com, 2005.

Last Updated: July 31, 2007