A systematic review of global leptospirosis morbidity and mortality estimates was conducted, revealing that approximately 1.03 million cases and 58,900 deaths occur annually worldwide. The disease is most prevalent in tropical and subtropical regions, with the highest burden in South and Southeast Asia, Oceania, the Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa. Adult males aged 20–49 years account for a significant proportion of cases and deaths. The study used regression models and Monte Carlo simulations to estimate disease burden, incorporating factors such as population structure, life expectancy, and urbanization. The findings highlight the need for improved diagnostics, surveillance, and control measures in resource-poor regions. Leptospirosis is a leading zoonotic cause of morbidity and mortality, with severe cases often leading to pulmonary hemorrhage and acute kidney injury. The study underscores the importance of addressing environmental and social factors contributing to the disease's spread, particularly in urban slums and areas with poor sanitation. The results emphasize the need for targeted interventions to reduce the burden of leptospirosis in high-risk populations.A systematic review of global leptospirosis morbidity and mortality estimates was conducted, revealing that approximately 1.03 million cases and 58,900 deaths occur annually worldwide. The disease is most prevalent in tropical and subtropical regions, with the highest burden in South and Southeast Asia, Oceania, the Caribbean, Andean, Central, and Tropical Latin America, and East Sub-Saharan Africa. Adult males aged 20–49 years account for a significant proportion of cases and deaths. The study used regression models and Monte Carlo simulations to estimate disease burden, incorporating factors such as population structure, life expectancy, and urbanization. The findings highlight the need for improved diagnostics, surveillance, and control measures in resource-poor regions. Leptospirosis is a leading zoonotic cause of morbidity and mortality, with severe cases often leading to pulmonary hemorrhage and acute kidney injury. The study underscores the importance of addressing environmental and social factors contributing to the disease's spread, particularly in urban slums and areas with poor sanitation. The results emphasize the need for targeted interventions to reduce the burden of leptospirosis in high-risk populations.