Vibrio mimicus, named because of its close metabolic and genetic similarity to V. cholerae, is recognized globally as a cause of foodborne and waterborne diarrheal disease (1–4). Limited data indicate that V. mimicus incidence is lower than that reported for V. parahaemolyticus and non-O1/non-O139 V. cholerae but comparable to that of V. fluvialis (3,4). Although some V. mimicus strains produce cholera toxin (CTX) or a cholera-like toxin or have genes from the ctx complex, most do not (1,5). Nonetheless, V. mimicus can cause severe, cholera-like illness; the hospitalization rate among case-patients reported in 2014 (the most recent year for which data are available) to the Centers for Disease Control and Prevention is 57% (3). We report a seafood-associated outbreak caused by V. mimicus in Florida, USA, in which 4 of 6 patients required hospitalization