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Background: In May of 2022, an mpox (formerly known as monkeypox) outbreak was reported from countries where the disease is not endemic, rising worldwide concern. Malta, the smallest European Union member state, faced unique challenges, with high infection rates compared to the rest of Europe. The aim of the study is to describe the clinical characteristics, diagnostic challenges, and unique demographics of mpox patients diagnosed in Malta., Methods: This is a retrospective analysis of medical records of all mpox cases recorded from May to September 2022. Demographic data, sexual behaviors and practices, travel history, comorbidities, and HIV status were investigated., Results: In the study period, we recorded 33 mpox cases, 97% of them were male, in the age group 30-39 (39%). Ninety percent were gay or bisexual men and 76% non-Maltese. The most common clinical presentations included skin rash (78%), lymphadenopathy (71%), anogenital lesions (67%), and fever (67%). Twenty-seven percent of the patients were people living with HIV. In terms of coinfection with STIs, 27% of patients tested positive for gonorrhea, 12% for syphilis, 15% for chlamydia, 9% for herpes simplex virus, and 3% for hepatitis C virus., Conclusion: The results shed light on unique challenges faced by the local sexual health clinic and call for more resources in response to the global emerging of infectious diseases., (© 2023 the International Society of Dermatology.)