Invasive infection and extraintestinal complications are rarely caused by Plesiomonas shigelloides, a waterborne bacterium implicated in gastroenteritis. Recent evidence from several reports suggests its importance in causing opportunistic infections in immunocompromised hosts. We report a case of P shigelloides bacteremia and epididymo-orchitis in a patient with HIV infection and chronic hepatitis C. This case illustrates a novel site of involvement by P shigelloides and underscores its role as an opportunistic pathogen.