A global outbreak of monkeypox virus infections in human beings has been described since April 2022. The objectives of this study were to describe the clinical characteristics and complications of patients with a monkeypox infection. All consecutive patients with a polymerase chain reaction (PCR)–confirmed monkeypox infection seen in a French referral centre were included. Between 21 May and 5 July 2022, 264 patients had a PCR-confirmed monkeypox infection. Among them, 262 (262/264, 99%) were men, 245 (245/259, 95%) were men who have sex with men, and 90 (90/216, 42%) practiced chemsex in the last 3 months. Seventy-three (73/256, 29%) patients were living with human immunodeficiency virus infection, and 120 (120/169, 71%) patients were taking pre-exposure prophylaxis against human immunodeficiency virus infection. Overall, 112 (112/236, 47%) patients had contact with a confirmed monkeypox case; it was of sexual nature for 95% of the contacts (86/91). Monkeypox virus PCR was positive on the skin in 252 patients, on the oropharyngeal sample in 150 patients, and on blood in eight patients. The majority of patients presented with fever (171/253, 68%) and adenopathy (174/251, 69%). Skin lesions mostly affected the genital (135/252, 54%) and perianal (100/251, 40%) areas. Overall, 17 (17/264, 6%) patients were hospitalized; none of them were immunocompromised. Complications requiring hospitalization included cellulitis (n = 4), paronychia (n = 3), severe anal and digestive involvement (n = 4), non-cardia angina with dysphagia (n = 4), blepharitis (n = 1), and keratitis (n = 1). Surgical management was required in four patients. The current outbreak of monkeypox infections has specific characteristics: it occurs in the men who have sex with men community; known contact is mostly sexual; perineal and anal areas are frequently affected; and severe complications include superinfected skin lesions, paronychia, cellulitis, anal and digestive involvement, angina with dysphagia, and ocular involvement.