Staphylococcus aureus is a leading cause of community acquired bacteremia and infective endocarditis. S. aureus is a part of the normal skin flora in approximately one third of the human population. Infective endocarditis due to S. aureus can cause several complications and is associated with increased mortality. A 48-year-old female with no significant medical history presented with S. aureus bacteremia and native mitral valve endocarditis. Multiple cutaneous skin lesions were identified, which she reported were due to recent bed bug bites. No source of infection was found except for the skin lesions. Her hospital course was complicated by pulmonary and cerebral septic emboli, left pleural empyema, and acute renal injury. We suspected the bed bug skin bites were the most likely source of bacteremia. Bed bugs carry many human pathogens but have not been shown to be a competent vector. We did not find any literature on endocarditis associated with bed bug bites; thus, our case will be a novel finding.