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This study assesses the preparedness of 17 health districts in the Littoral region (Cameroon) for a possible Mpox epidemic. Conducted from August to September 2024, it reveals that 29% of districts are insufficiently prepared, 17% limited, 41% average and only 11% good. The main obstacles include the absence of a response plan, lack of financial and material resources, inadequate diagnostic capabilities and lack of staff training. In order to prevent a possible Mpox epidemic in the health districts of the Littoral region, it is essential to strengthen district preparedness in terms of response coordination and management, case management, risk communication and community involvement, prevention and control measures, integrating a differentiated approach taking into account disparities between districts.