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Background: Rhabdomyolysis has multiple etiologies with unclear mechanisms; however, rhabdomyolysis caused by Staphylococcus aureus infection is rare., Case Report: A case report of severe rhabdomyolysis in a patient who presented with endocarditis caused by methicillin-susceptible S. aureus and review of relevant literature., Results: The patient had a history of cardiac surgery for tetralogy of Fallot. He was admitted to the hospital because of fever and digestive symptoms. Respiratory and hemodynamic status deteriorated rapidly, leading to admission to the intensive care unit (ICU) for mechanical ventilation and vasopressor support. Laboratory tests disclosed severe rhabdomyolysis with a serum concentration of creatine kinase that peaked at 49,068 IU/L; all blood cultures grew methicillin-susceptible S. aureus. Antibiotic therapy was amoxicillin-clavulanic acid, ciprofloxacin, and gentamicin initially and was changed subsequently to oxacillin, clindamycin, and gentamicin. Transesophageal echocardiography showed vegetation on the pulmonary valve, thus confirming the diagnosis of acute endocarditis. Viral testing and computed tomography (CT) scan ruled out any obvious alternative etiology for rhabdomyolysis. Bacterial analysis did not reveal any specificity of the staphylococcal strain. The patient improved with antibiotics and was discharged from the ICU on day 26. He underwent redux surgery for valve replacement on day 53., Conclusions: Staphylococcal endocarditis should be suspected in cases of severe unexplained rhabdomyolysis with acute infectious symptoms.