We report a case of acute, self-resolving leptospirosis presenting in a HIV-positive patient from the Peruvian Amazon. The patient presented with an undifferentiated acute febrile illness that resolved without treatment, diagnosed retrospectively as leptospirosis by serology and real-time polymerase chain reaction. Five months later, he was admitted because of a febrile illness with jaundice, hepatosplenomegaly, peripheral edema, and oral candidiasis. Because of the clinical suspicion of AIDS, stored sera of the previous admission were tested, and HIV seropositivity was confirmed, proving that the condition was present at the first admission. Acute leptospirosis in HIV coinfection is not inevitably severe, and there is probably a wide variation in clinical manifestations similar to what occurs in immunocompetent hosts. Copyright © 2005 by The American Society of Tropical Medicine and Hygiene.