To describe prevalence of fatigue and its correlates among persons with HIV infection, we abstracted medical records of 13,768 persons in care for HIV in >100 US clinics. The prevalence of fatigue (defined as fatigue, malaise, or weakness that was the primary reason for a medical visit, was persistent, or was severe enough to preclude work) was 37%. Fatigue was more common among persons with clinical AIDS (adjusted odds ratio [AOR] 1.3, CI 1.1–1.5); depression (AOR 2.4, CI 2.1–2.7); and hemoglobin concentrations <8, 8–10, and 10–12 g/dL (AORs 3.3 [CI 2.4–4.6], 2.7 [CI 2.2–3.2], and 1.5 [CI 1.3–1.7], respectively). Fatigue was not associated with viral load or CD4 cell count <200/μl. Fatigue cannot be viewed solely as a constitutional symptom of progressive HIV disease. Physicians should seek underlying, treatable causes for fatigue such as depression and anemia and treat these conditions when they are found.