Southern sea otters (Enhydra lutris nereis) from the California coast continue to exhibit a slower population regrowth rate than the population in Alaska. Infectious diseases have been identified as a frequent cause of death. Infectious diseases caused by varied pathogens including bacteria, fungi, and parasites were suggestive of compromised immunological health of mature animals in this population. To test the hypothesis that elevated exposure to immunotoxic contaminants such as polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) contribute to disease susceptibility via immunosuppression, we determined concentrations of PBDEs and PCBs in livers of 80 adult female sea otters that died of infectious diseases, noninfectious causes, or emaciation. Concentrations of PBDEs and PCBs in sea otter livers varied widely (10–26,800 ng/g and 81–210,000 ng/g, lipid weight, respectively). Concentrations of PBDEs in sea otters were some of the highest values reported for marine mammals so far. Although PCB concentrations in sea otters have declined during 1992-2002, the mean concentration was at the threshold at which adverse health effects are elicited. Concentrations of PBDEs and PCBs were significantly correlated, suggesting co-exposure of these contaminants in sea otters. No significant association was found between the concentrations of PBDEs and the health status of sea otters. Concentrations of PCBs were significantly higher in otters in the infectious disease category than in the noninfectious category, suggesting an association between elevated PCB concentrations and infectious diseases in Southern sea otters.