Cryptococcal endocarditis is an exceedingly rare entity associated with high mortality and morbidity. Hereby, we present a 37-year-old patient with underlying systemic lupus erythematosus and end-stage renal disease who was diagnosed with cryptococcal endocarditis involving native mitral valve. Her blood culture grew Cryptococcus neoformans. Echocardiography confirmed presence of vegetations and patient underwent mitral valve replacement and received appropriate anti-fungal treatment. Her course was further complicated by sternal wound dehiscence and infection of hemodialysis site as well as atrial flutter. Unfortunately, patient passed 2 weeks after discharge from hospital. C. neoformans is typically known to cause serious central nervous system. However, this pathogen can rarely cause serious infective endocarditis case particularly in immune compromised patients or those with prosthetic valves. Fungal endocarditis is usually treated with a combination of surgery and anti-fungal medications.