Variation in the intensity of fatigue according to selected demographic, cultural, and health/illness variables was explored in 372 patients with HIV/AIDS, and the contribution of fatigue to physical and mental health in this population was investigated within the UCSF Symptom Management Model (UCSF-SMM). The sample included 73% African Americans and 63% males. Moderate to severe fatigue intensity was reported by 58% of the total sample. Women, Hispanics, the disabled and those with inadequate income or insurance reported higher fatigue intensity scores. Two hierarchical regression models explored the contributions of fatigue to physical and mental health. Fatigue contributed 2% to the total variance (37.4%) in physical health, but did not contribute as an independent predictor of the total variance (23.2%) in mental health. The results of this study imply the need for further gender and ethnic-specific fatigue research, as well as symptom cluster research.