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Key Clinical Message Leptospirosis is an important zoonosis worldwide. Due to nonspecific clinical manifestation and poor recognition in non‐epidemic area, there is often a delay in diagnosis and treatment. Early diagnosis from Metagenomic next‐generation sequencing test is crucial for timely intervention. Abstract We presented a case of a 19‐year‐old male patient who developed leptospirosis infection characterized by acalculous cholecystitis and septic shock after typhoon events. Metagenomic next‐generation sequencing (mNGS) helped to early diagnose leptospirosis infection. Finally, the patient achieved full recovery following the antibiotic treatment in addition to supportive care and was discharged.