Background: On 23 July 2022, the World Health Organization (WHO) declared the mpox multi-country outbreak as a Public Health Emergency of International Concern. This study aimed to identify the epidemiological and clinical characteristics of confirmed mpox cases reported in Serbia in 2022. Methods: The mpox WHO case definition was used. Incidence rates (IRs) and incidence rate ratios (IRRs) by age groups and nomenclature of territorial units for statistics level 3 (NUTS-3) with 95% confidence intervals (CIs) were calculated. Results: Between June and October 2022, 43 laboratory-confirmed cases were reported. All were unvaccinated males, with the mean age of 34 (±7.4) years. Out of the total, 72.1% cases were men who have sex with men (MSM), who reported sexual intercourse either with multiple or unknown partners (p < 0.01). Fifteen cases (34.9%) lived with HIV, mostly in the 30–39 age group (p = 0.023). People living in Belgrade City NUTS-3 were six times more likely to become infected compared to South Backa citizens (IRR: 6.03, 95% CI: 1.47–25.53). Conclusions: In Serbia, mpox mainly affected MSM aged 30–39 and living in urban areas. Health promotion and vaccine implementation should be prioritized in populations with a higher risk
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