Histoplasmosis is a systemic fungal infection caused by dimorphic fungus, Histoplasma capsulatum. Immunocompetent individuals usually have self-limiting or localized disease whereas immunocompromised individuals develop disseminated disease. The occurrence of progressive disseminated histoplasmosis in juvenile systemic lupus erythematosus is extremely rare with only one reported case in literature showing such association. Therefore, we report a case of severe opportunistic fungal infection caused by Histoplasma in a 13-year-old girl who was diagnosed with juvenile lupus erythematosus, subsequently developed septic shock and died of the disease despite of aggressive antifungal therapy.