Brazil was one of the countries most affected by the multinational mpox outbreak, with a disproportionate burden among men who have sex with men and people with HIV (PHIV). PHIV and individuals with advanced immunosuppression may develop severe and prolonged forms of the disease, which can be further complicated by the use of immunosuppressants after organ transplantation. We report the case of a PHIV and kidney transplant recipient diagnosed with mpox in Rio de Janeiro. This is a 53-year-old cisgender man diagnosed with HIV in 2011, with sustained viral suppression since then, who underwent kidney transplantation in 2021 due to chronic kidney disease of unknown cause. In February 2025, he sought medical care with an 8-day history of disseminated skin lesions, without other symptoms. Examination showed 87 polymorphic lesions, bilateral inguinal lymphadenopathy, mucosal lesions in the oropharynx and penis, foreskin edema and balanoposthitis. He was taking 3TC/DTG, tacrolimus 2 mg/day, mycophenolate sodium 1440 mg/day and prednisone 5 mg/day with good adherence. Initial assessment showed undetectable HIV viral load and CD4+ count of 531 cells/mm³. Monkeypox virus RT-PCR was positive in skin lesion swabs [Ct first sample 15.57 and Ct second sample 19.27], oropharyngeal swab [Ct 29.24] and rectal swab [Ct 30.7]. Due to immunosuppression, tecovirimat (600 mg orally every 12 hours for 14 days) was started immediately, along with antibiotics for balanoposthitis. Despite the expected drug interaction between tecovirimat and tacrolimus, the immunosuppressant dose was maintained with serum level monitoring. During the course, there was worsening of genital lesions and renal function, prompting a 6-day hospitalization for pain control, hydration and wound care. After discharge, the patient showed partial improvement, with a persistent penile ulcer that healed after 79 days. Renal function fully recovered, with no need to adjust the immunosuppressant dose. This case shows that a severe and prolonged presentation of mpox may occur even in PHIV with well-controlled immunovirological status when there is concomitant drug-induced immunosuppression due to transplantation. Tecovirimat remains the most widely used antiviral in severe cases, although efficacy data are limited, and it may be considered for immunosuppressed individuals not related to AIDS, as long as that potential interactions, particularly with calcineurin inhibitors, are carefully monitored.