BackgroundLeptospirosis is an emerging neglected tropical zoonotic disease of public health importance causing substantial morbidities and mortalities among humans. The infection is maintained within the population through interactions between humans, animals, and the environment. Understanding the burden of disease in both humans and animals is necessary for effective prevention and control in Sub-Saharan Africa (SSA). Therefore, we aimed to determine the seroprevalence of leptospirosis in humans, selected domestic animals, and rodents in SSA.MethodsA comprehensive search was done in six databases: Scopus, PubMed, Google Scholar, CINAHL, Web of Science, and African Journals Online databases for articles published between 01 January 2014 and 30 August 2022. Thirty-seven articles distributed across 14 out of 46 countries in SSA were included. The random effects meta-analysis model was used to pool the extracted seroprevalence data.ResultsThe overall pooled seroprevalence of leptospirosis among humans was 12.7% (95% CI: 7.5,20.8), 15.1% (95% CI: 9.4,23.5), and 4.5% (95% CI: 0.4, 35.6) based on results obtained using ELISA, MAT, and PCR diagnostic methods respectively. The pooled seroprevalence estimates among cattle were 29.2%, 30.1%, and 9.7% based on ELISA, MAT, and PCR respectively. Further, the pooled seroprevalence in goats was 30.0% for studies that used MAT, and among rodents, the pooled seroprevalence estimates were 21.0% for MAT and 9.6% for PCR diagnostic criteria. The seroprevalence of leptospirosis varied extensively between studies, across SSA regions and study setting (rural or urban).ConclusionLeptospirosis is widespread in SSA in both humans and animals based on the current results of the pooled seroprevalence in the limited studies available. The burden is high in animals and humans and underestimated due to limited studies and challenges with limited diagnostic capacity in most healthcare settings in SSA. Hence, we recommend that leptospirosis should be listed as a disease of concern and be included on the list of routine diagnostics among patients presenting with febrile illness in healthcare settings. Further, we recommend the enhancement of surveillance of leptospirosis in all countries in SSA and the development of strategies with a One Health perspective to effectively prevent and control leptospirosis.