BACKGROUND Envenomation from the brown recluse spider (Loxosceles reclusa) is described to cause both local and systemic symptoms. We report a case of an adolescent boy who developed severe systemic loxoscelism, and his clinical course was complicated by myocarditis, which has not been previously reported in association with loxoscelism. CASE REPORT A 16-year-old boy presented with non-specific symptoms and forearm pain following a suspected spider bite, which subsequently evolved into a necrotic skin lesion. During his clinical course, he developed a characteristic syndrome of systemic loxoscelism with hemolysis, disseminated intravascular coagulopathy, and severe systemic inflammatory response syndrome, necessitating transfer to the Intensive Care Unit. The diagnosis was confirmed with an enzyme-linked immunosorbent assay that detected Loxosceles venom in the wound. Additionally, he developed pulmonary edema and cardiogenic shock secondary to myocarditis, which was confirmed with cardiac magnetic resonance imaging. Steroids and plasmapheresis were initiated to manage the severe inflammatory syndrome, and the myocarditis was treated with intravenous immunoglobulins, resulting in resolution of symptoms and improvement of cardiac function. CONCLUSIONS This is the first reported case of myocarditis associated with loxoscelism, providing evidence for Loxosceles toxin-associated cardiac injury, which has been previously described in animal models only. Furthermore, this case provides further support for the use of confirmatory testing in the clinical diagnosis of loxoscelism.