Scientists do not know what causes chronic fatigue syndrome (CFS). It was once thought to be caused by infection with Epstein-Barr virus (EBV) or another virus and used to be referred to as chronic EBV. However, it is now believed that CFS cannot result from infection with any one known human pathogen, though infectious agents may play a role in some cases of CFS, according to the National Center for Infectious Diseases.

Some CFS patients have signs of autoimmune diseases, such as autoantibodies (immune system proteins that mistakenly attack the body’s healthy tissues). However, tissue damage characteristic of autoimmune disorders has not been described in people with CFS.

Several studies indicate that the central nervous system has a role in CFS. For example, CNS dysfunction may impair the immune system or inhibit the release of pain-relieving hormones such as cortisol. More research would be needed to establish a link.

In addition to researching possible roles of viruses and the immune and nervous systems, scientists are studying other possible factors, including genetic predisposition, stress, metabolic disturbances, hormones and environment. Recent research has suggested that genetics might impair CFS patients' ability to cope with physical and psychological stress.

According to the National Women’s Health Resource Center, one-third of cases follow a symptomatic respiratory, stomach or other acute infection, and other cases develop after physical or emotional trauma such as surgery, a car accident or the death of a loved one. Some research has linked a sedentary lifestyle to increased risk of CFS.

In spite of different speculations, the exact cause of CFS remains unknown.

The primary known risk factors for chronic fatigue syndrome are sex and age. Three to four times as many women as men have CFS, and the condition seems to be most common in women in their 40s, according to the National Women’s Health Resource Center. The condition can occur at any age and has also been described in young adults and adolescents.