From 2002 to 2006, eight captive southern sea otters (Enhydra lutris nereis) at research and display institutions in California at risk of exposure to potentially lethal morbiliviruses were vaccinated with a commercial recombinant poxvirus vectored canine distemper (CD) vaccine. Serum-neutralizing (SN) antibody responses were followed for several years. The goal of this study was to determine whether 1) CD vaccination was a safe preventive medicine procedure for this species; 2) sea otters produce detectable SN antibodies in response to vaccination with this product; and 3) if this type of vaccination might be useful in response to a morbilivirus disease outbreak in free-ranging sea otters. Results indicate that a commercial recombinant vaccine is safe, provokes a measurable SN antibody response, and that vaccination may provide some protection from infection for free-ranging sea otters. It also resulted in the reevaluation of CD serology data that were previously published for free-ranging sea otters.