Salmonella infections are responsible for a large burden of disease worldwide. Non-typhoidal Salmonella (NTS) species cause a myriad of disease manifestations, particularly amongst severely immunocompromised individuals. We present a rare case of endocarditis caused by the NTS species Salmonella Enteritidis in an individual living with HIV and hepatitis C. In this case, endocarditis was complicated by embolization and acute arterial occlusion of the left arm, as well as mitral valve perforation resulting in cardiac failure. A review of the available literature shows few cases of NTS causing endocarditis in people living with HIV, with the earliest reported case in 1983. Our case demonstrates the potential complications of NTS endocarditis and highlights the importance of evaluating patients with NTS-associated blood stream infection for cardiovascular involvement. Prompt surgical intervention in addition to appropriate antimicrobial therapy is essential to reduce the high morbidity and mortality associated with NTS endocarditis.