Laguna de Terminos, a wide coastal lagoon system in Campeche, Mexico, was investigated for the contamination by polychlorobiphenyls (PCBs). Distribution of these industrial chemical contaminants along with pesticide residues in the lagoon, as well as their sediment–water partitioning and bioaccumulation by oysters and fish were assessed. Contaminant concentrations in the lagoon were compared with toxicity data for aquatic organisms and the ecotoxicological risks discussed. Current contaminant concentrations generally were several orders of magnitude below acute toxic levels for the most sensitive aquatic species and this seems compatible with the status of nature reserve and functions aimed at Laguna de Terminos. In particular, Penaeidae shrimp species that are the most valuable fisheries resources of Campeche with important populations in the Laguna are not impaired with the current low levels of these contaminants. Nevertheless, due to known environmental persistence, the surveillance of chlorinated contaminant levels in the lagoon ecosystems is recommended.