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© 2022 The Authors. Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/), Human monkeypox (MPX) is an endemic zoonotic disease in regions of Africa caused by the monkeypox virus, with recent outbreaks in several non-African countries. In this study, we present two cases of patients with MPX infection complicated by a deep skin infection. Both patients presented to our dermatology clinic with a clinical syndrome characteristic of MPX. The diagnosis was confirmed based on swabs of skin lesions. Both patients later returned to our clinic with erythema, pain, and edema at the site of previous papules and were diagnosed with deep skin bacterial infection. In this study we provide information on what we believe was an underreported MPX infection complication and give some advice on preventing cases of cellulitis in these patients.