Zebra mussel (Dreissena polymorpha) is an invasive species that has proliferated in European and North American rivers and lakes during the last century. In this study, D. polymorpha has been used to provide information on contamination levels and biological effects in the Seine Estuary (France). The bivalves accumulated polychlorinated biphenyls (PCBs) and polycyclic aromatic hydrocarbons (PAHs) to a high degree with values reaching 800 ng/g dry weight for PCBs (sum of 20 congeners), and 1,000 ng/g dry weight of PAHs (sum of 14 compounds) in the whole body. These values are among the highest reported of PCBs and, to a lesser extent, of PAHs in other contaminated areas in the world. Toxic equivalent quantities of PCBs and PAHs detected in zebra mussels varied from 20 to 40 pg dioxin equivalents/g dry weight for PCBs and up to 120 ng benzo[alpha]pyrene equivalents/g dry weight for PAHs, indicating a high potential risk for animals feeding on them. Biological impacts, such as altered condition index, decreased lysosomal stability, and high levels of multixenobiotic resistance (MXR) proteins also were detected in mussels living downstream of Rouen, the main city of the Seine Estuary. Taken together, these results indicate that the Seine Estuary is a heavily polluted area with the potential to cause deleterious health effects in some endogenous living organisms. This study also shows that chemical and biological measurements bring different but complementary results that can help diagnose environmental health.