Foot-and-mouth disease (FMD), is a highly contagious viral disease affecting livestock. It is manifested by fever and blisters in the mouth, on the teats, and between the hooves. This study was conducted in the Northern Cameroon, to assess the seroprevalence and economic impact of foot-and-mouth disease (FMD) in small ruminants. A total of 175 breeders were investigated and 63 serum samples were extracted from small ruminants for to detect antibodies against nonstructural proteins of the foot-and-mouth virus using the ELISA competition technique. The overall morbidity rate of foot-and-mouth disease was 96.13%. The estimated mortality rates were 20.05% in sheep and 24.22% in goats. Young lambs in the Far North had a high rate of morbidity (73.69%) and mortality (35.30%) rates compared to other regions. Total economic losses associated with the disease were high in the North and Far North regions, averaging of 433,526 ± 400,896 FCFA and 386,882 ± 577,742 FCFA respectively. Mortality losses were higher in the Far North, averaging 254 540 ± 391 655 FCFA which differs significantly from the other two regions (P < 0.05). Of the 63 analyzed, 30 were positive, resulting in an overall seroprevalence of 47.61%. The positive sample were susceptible to serotype O of aphtovirus. Due to the significant losses associated with FMD, it is crucial to rigorously implement the national program to combat this disease.