ABSTRACT Monkeypox (MPX) transmission outside non-endemic countries has been reported since May 2022, rapidly evolving into a multi-country outbreak. A potential role of sexual contact in transmission dynamics, as well as a predominance of anogenitallesions, are remarkable features of current cases. Screening for sexually transmitted infections (STIs) plays an important role in the evaluation of patients with suspected MPX infection. Herein we report the first case of a patient diagnosed with both MPX and acute HIV infection in Latin America. He had no major complications during his clinical course, and antiretroviral therapy was promptly initiated. Diagnosis of acute HIV requires a high level of suspicion and appropriate laboratory investigation. Health practitioners need to consider this diagnosis while evaluating patients with suspected MPX with a recent unprotected sexual contact.