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Background: Leptospirosis poses a diagnostic challenge owing to its wide array of symptoms, ranging from asymptomatic cases and febrile syndromes to severe disease with a high mortality rate. Risk factors are associated with exposure and the immune response, particularly in immunosuppressed patients. Case presentation: A clinical case involving a 49-year-old patient with a history of splenectomy and no immunization schedule. The patient presented to the emergency room with non-specific symptoms, primarily myalgias, arthralgias, and emesis, initially suggestive of a viral infection. However, there was a rapid progression to hypoxemic respiratory failure, requiring invasive ventilatory support. Given the immune status due to spleen absence, antibiotic treatment with meropenem and linezolid was promptly initiated, to mitigate the risk of post-splenectomy sepsis. During antibiotic administration, the patient experienced febrile episodes, accompanied by chills, myalgias, and emesis, which gradually decreased in both duration and intensity. Ultimately, the patient exhibited satisfactory progress, successfully underwent extubation, and completed a 7-day antibiotic course. Final reports confirmed positive IgM for Leptospira. Conclusion: Leptospirosis is a global zoonotic disease, displaying a diverse array of manifestations; recognized as a potential cause of undifferentiated fever, often confused with other prevalent tropical infections. The imperative to consider this diagnosis extends beyond the general population to encompass individuals in states of altered immunity. Recognizing and addressing leptospirosis in at-risk populations is crucial, as it can significantly impact the prompt initiation of treatment and, consequently, influence associated mortality rates. [ABSTRACT FROM AUTHOR]