A monkeypox virus outbreak has been spreading in multiple nonendemic countries since May 2022. The atypical clinical profile of patients has led to a very likely underestimation of the number of cases at the beginning of the epidemic. The detection and quantification of the Monkeypox virus genome in sewersheds in Paris (France) correlated temporally with the identification of the first case of infection and the spread of the disease within the population connected to the sewage system.