Despite the fact that fatigue is a common and debilitating symptom among HIV-infected persons, we know little about the predictors of fatigue in this population. The goal of this cross-sectional study was to examine the effects of early childhood trauma, recent stressful life events and depression on intensity and impairment of fatigue in HIV, over and above demographic factors and clinical characteristics. We studied 128 HIV-infected men and women from one southern state. The median number of childhood traumatic events was two and participants tended to have at least one moderate recent stressful event. Multiple regression findings showed that patients with less income, more childhood trauma, more recent stressful events and more depressive symptoms had greater fatigue intensity and fatigue-related impairment in daily functioning. Recent stresses were a more powerful predictor of fatigue than childhood trauma. None of the disease-related measures (e.g. CD4, viral load, antiretroviral medication) predicted fatigue. Although stress and trauma have been related to fatigue in other populations, this is the first study to examine the effects of traumatic and recent stressful life events on fatigue in an HIV-infected sample.