Lesions consistent with exertional myopathy (EM) were documented postmortem in four North American river otters (Lutra canadensis) during translocation for a population restoration project. Clinical signs in these otters included depression, anorexia and shock. Gross lesions in one otter included locally extensive linear, pale areas within the subscapularis, rectus abdominis, quadriceps, and dorsal laryngeal muscles. Microscopic lesions were characterized by acute to subacute myofiber necrosis of varying severity, and occurred in a variety of skeletal muscles as well as cardiac muscle in one otter. Based on these observations, we conducted a retrospective review of records of otters which experienced similar capture, transfer, and holding protocols between 1995 and 1997, but with a successful outcome (n = 69). Significant elevations in serum aspartate aminotransferase (AST) and creatine kinase (CK) were observed in 19 (28%) of the otters, but may have been higher due to delayed sample collection from some otters. However, none of the otters with elevated enzymes exhibited clinical signs suggestive of EM. These findings indicate that river otters may develop EM when translocated, but many cases may be mild or clinically inapparent.