Leptospirosis, a zoonotic bacterial disease, affects vulnerable populations such as rural subsistence farmers and urban slum dwellers. Despite its life-threatening nature and recognition as a significant cause of pulmonary hemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected status. This systematic review aimed to estimate the global burden of leptospirosis by analyzing published morbidity and mortality studies and databases. The review identified 80 studies on disease incidence from 34 countries, with a significant proportion of cases and deaths occurring in adult males aged 20-49 years. The estimated annual global incidence was 1.03 million cases (95% CI 434,000-1,750,000), and 58,900 deaths (95% CI 23,800-95,900). The highest morbidity and mortality were observed in resource-poor countries, particularly in regions where surveillance is underdeveloped. The study highlights the need for improved diagnostics, surveillance, and control measures to address the neglected disease status of leptospirosis.Leptospirosis, a zoonotic bacterial disease, affects vulnerable populations such as rural subsistence farmers and urban slum dwellers. Despite its life-threatening nature and recognition as a significant cause of pulmonary hemorrhage syndrome, the lack of global estimates for morbidity and mortality has contributed to its neglected status. This systematic review aimed to estimate the global burden of leptospirosis by analyzing published morbidity and mortality studies and databases. The review identified 80 studies on disease incidence from 34 countries, with a significant proportion of cases and deaths occurring in adult males aged 20-49 years. The estimated annual global incidence was 1.03 million cases (95% CI 434,000-1,750,000), and 58,900 deaths (95% CI 23,800-95,900). The highest morbidity and mortality were observed in resource-poor countries, particularly in regions where surveillance is underdeveloped. The study highlights the need for improved diagnostics, surveillance, and control measures to address the neglected disease status of leptospirosis.