Human monkeypox (mpox) is usually self-limited infection; however, rising data show a worse outcome in patients with impaired immune status, particularly those co-infected with HIV [Mitjà O, Alemany A, Marks M, Lezama Mora JI, Rodríguez-Aldama JC, Torres Silva MS et al. Mpox in people with advanced HIV infection: A global case series. Lancet. 2023; 401:939-49. DOI:https://doi.org/10.1016/S0140-6736(23)00273-8] [Govind A, Lazarte SM, Kitchell E, Chow JY, Estelle CD, Fixsen E et al. Severe mpox infections in people with uncontrolled human immunodeficiency virus (HIV). Clin Infect Dis. 2023; 76:1843-6. DOI:https://doi.org/10.1093/cid/ciad052].We report the clinical, pathological, and molecular study of a patient with mpox infection and a late HIV diagnosis, with fatal outcome.Necropsy revealed visceral spread of mpox. Mpox virus was sequenced twice during the admission, uncovering an emerging mutation near a genomic region where mutations associated with tecovirimat resistance have been documented.Monkeypox can manifest as an opportunistic infection in individuals with advanced HIV-associated immunosuppression.