Introduction: Leptospirosis can be associated with multi-system organ failure (MSOF) and significant morbidity and mortality. Extracorporeal life support (ECLS) has been used as salvage therapy for severe leptospirosis complicated by acute respiratory distress syndrome (ARDS). Current knowledge in this field is limited, with no standardized treatment approaches. We aim to describe the literature to date on the use of ECLS in patients with leptospirosis, highlighting associations, outcomes, and complications. Methods: We report on the successful use of ECLS in two cases of severe leptospirosis and conduct a narrative review of the literature. Using a search strategy developed in consultation with a medical librarian and validated across pre-selected articles, several databases were searched. We included case reports, case series, cohort studies, and prospective studies of adult patients with confirmed leptospirosis undergoing ECLS. Editorials, surveys, or opinion articles without primary patient data were excluded. Overall mortality was our primary outcome. Results: Two cases of previously healthy males presenting with ARDS due to leptospiral infection are described. Literature review identified 25 articles containing 43 reported cases of patients treated with ECLS for severe leptospirosis. Patients were mostly young and male. Overall mortality was 16%. The most common complication recognized was acute renal failure requiring renal replacement therapy. Additional complications included diffuse intravascular coagulation, necrotizing pancreatitis, and limb ischemia. Conclusion: Leptospirosis should be considered in patients with epidemiologic exposure(s) presenting with critical illness, including ARDS and MSOF. ECLS is a viable rescue strategy in severe leptospirosis, even with established MSOF.