A previously healthy, 39-year-old obese farmer, arrived hypotensive and tachycardic, with fever, myalgia, headache, abdominal pain, diarrhea, and progressive dyspnea. Ten days before symptoms onset, he was in direct contact with mice and working in a contaminated drain. Patient laboratory showed acute kidney injury and thrombocytopenia. Chest X-ray exhibited bilateral diffuse interstitial infiltrates. First-line empirical antibiotics were started and influenza discarded. Patient evolved with severe respiratory failure, associated with hemoptysis, and rapidly severe hemodynamic compromise. Despite neuromuscular blockade and prone positioning, respiratory failure increased. Accordingly, veno-venous ECMO was initiated, with bilateral femoral extraction and jugular return. After ECMO connection, there was no significant improvement in oxygenation, and low pre-membrane saturations and low arterial PaO2 of the membrane showed that we were out of the limits of the rated flow. Thus, a second membrane oxygenator was installed in parallel. Afterward, oxygenation improved, with subsequent perfusion enhancement. Regarding etiology, due to high suspicion index, Leptospira serology was performed, coming back positive and meropenem was maintained. The patient ultimately recovered and experience excellent outcome. The clinical relevance of the case is the scared evidence of leptospirosis-associated severe respiratory failure treated with ECMO. This experience emphasizes the importance of an optimal support, which requires enough membrane surface and flow for an obese, highly hyperdynamic patient, during this reversible disease. A high index of suspicion is needed for an adequate diagnosis of leptospirosis to implement the correct treatment, particularly in the association of respiratory failure, pulmonary hemorrhage, and an epidemiological-related context.