Colombia is the fifth most affected country by the global monkeypox outbreak and the second in LAC after Brazil. We describe the clinical and epidemiological characteristics of 521 patients with mpox in the country.We conducted an observational analysis of laboratory-confirmed Mpox cases between June 29 and November 16, 2022.Most cases were young men living with HIV. The clinical evolution was primarily benign, with two deaths reported. We found some differences between women and men regarding their BMI, presence of lymphadenopathies, localization of lesions, and the antecedent of HIV infection.Although it seems that the epidemic curve for this outbreak of Mpox is decreasing not only in Colombia but globally, it could remain endemic. Therefore, it is necessary to maintain very close surveillance.