Tehran University of Medical Sciences Case Reports in Clinical Practice 2538-2683 9 4 2025 02 22 146 151 Kiana Razavi Student Research Committee, School of Medicine, Mazandaran University of Medical Sciences, Sari, Iran. Leila Shahbaznejad Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Azin Hajialibeig Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Reza Navaeifar Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Ali Sadeghi Lotfabadi Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. Mohammad Sadegh Rezai Pediatric Infectious Diseases Research Center, Communicable Diseases Institute, Mazandaran University of Medical Sciences, Sari, Iran. 2024 02 25 2024 11 30 While presentations of novel severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) were observed to be mild in children, multi-system inflammatory syndrome in children (MIS-C) has emerged as one of the most critical phenomena in the era of Coronavirus disease 2019 (COVID-19). We present an eight-year-old boy with prolonged fever, weakness, myalgia, arthralgia, oliguria, hematuria, hemoptysis, and periumbilical pain. With regards to the history of contact with SARS-CoV-2 four weeks prior to symptom onset and prominent gastrointestinal symptoms, MIS-C was highly suspected. Furthermore, based on the compatible symptoms and history of white-water rafting and exposure to contaminated soil two weeks prior to admission, leptospirosis was probable. Of note, Leptospirosis immunoglobulin M and COVID-19 immunoglobulin G were detectable. Lifesaving supportive measures, empirical antibiotic therapy, Remdesivir, Dexamethasone, and Prednisolone pulse therapy were prescribed. Afterward, gradual clinical improvement was shown. We aimed to report a case with MIS-C accompanied by severe leptospirosis to emphasize that in endemic areas of leptospirosis, considering the co-occurrence of MIS-C and other inflammatory disorders is crucial for multidisciplinary management. https://crcp.tums.ac.ir/index.php/crcp/article/view/924 https://crcp.tums.ac.ir/index.php/crcp/article/download/924/674