Chronic Fatigue Syndrome (CFS) is an illness characterized by fatigue with varying levels of disability. According to the Centers for Disease Control (CDC) there are 2 to 5 million people in the United States who suffer from CFS and a disproportionate number are women. There are many theories of etiology of the condition and controversy has surrounded recommendations for diagnosis and treatment. CFS can mimic other diseases and women are doubly affected since many have comorbid conditions. While diagnoses and treatment are critical to the health of women, having the disease and coping with the symptoms may have a greater impact on their well-being and quality of life. The authors report qualitative data describing the experience of having CFS (N = 22) and quantitative responses of 42 CFS sufferers reporting psychosocial factors. The psychosocial factors were measured by the Derogatis Stress Profile (DSP), Spielberger Trait-Anger Scale, Ways of Coping Survey, Profile of Moods States (POMS) Survey, and the Perceived Stress Scale. The findings indicate that CFS changes the lives of women who suffer with the disease and disrupts their relationships, careers, and perceptions of themselves.