BackgroundThis study assessed the current state of knowledge, including social determinants of health considerations, regarding mpox acquisition and severity in Southwest and Littoral regions, Cameroon.MethodsThis was a descriptive cross-sectional study carried out with mpox cases from Southwest and Littoral regions. Perceived knowledge and determinants of mpox were assessed via a self-reported questionnaire. Descriptive and inferential statistical analyses were performed.ResultsA total of 394 participants took part in the study. With respect to the socio-demographic characteristic of the study population, 356 (89.4%) were Cameroonians, 267 (67.1%) were females, and 261 (65.60%) were students. With regards to mpox knowledge, 278 (69.8%) of the respondents declared that mpox is caused by a virus, with 12 (3.0%) individuals responding that the signs and symptoms associated with mpox were back and/or muscle pain, skin rash, fever, pustules, and exhaustion. Knowledge scores were found to be dependent on socio-demographic background. Based on socio-behavioral determinants of mpox, 348 (87.4%) of the participants reported consumption of wild game (bushmeat) and 92 (23.1%) participants reported that mpox can be treated traditionally in their culture. Regarding epidemiological determinants, 42 (10.6%) participants reported that mpox can be transmitted through direct contact with lesions, 120 (30.2%) reported prior smallpox infection, and 47(11.8%) reported prior mpox infection. Based on risk factors reported, 180 (46.7%) of the participants had close contact with confirmed or probable cases of mpox and 196 (49.2%) were present in healthcare facilities where mpox cases were managed.ConclusionMultiple knowledge gaps regarding mpox and MPXV were documented in the population in Southwest and Littoral regions of Cameroon. Reported social and behavioral determinants included the state of instability of the southwest region and population displacement in the bushes/forests, wild game consumption without proper cooking and poor hygiene were associated with mpox infection risk perception and vulnerability. On the epidemiological aspects increased instability, travel out of town, and limited remote rural chickenpox vaccination coverage were reported to increase risk, vulnerability, and spread of mpox within these endemic communities.