Increasing activity along the French Atlantic coast has led to chronic pollution with, in particular, mixtures of contaminants such as hydrocarbons, phytosanitary products, PCBs and heavy metals. Based on previous research, pollution biomarkers were used in this study as they can indicate health status when monitoring the impact of pollutants on coastal species such as the marine bivalve Mimachlamys varia. Mollusc bivalves were sampled in March 2016, in open and semi-open areas (a harbour zone), from thirteen sites which differed in terms of their level of pollution, and were located along the Atlantic coast from Brittany down to the Nouvelle-Aquitaine region. First, analyses of heavy metals and organic contaminants (e.g. pesticides, polycyclic aromatic hydrocarbons, polychlorobiphenyl) in the digestive gland of bivalves were performed. Second, biochemical assays were used to study defence biomarkers: oxidative stress with Superoxide Dismutase (SOD), detoxification of organic compounds with Glutathione-S Transferase (GST), lipid peroxidation with Malondialdehyde (MDA), and immune processes with Laccase. In addition to the biochemical assays, a genetic approach was used to measure genetic diversity (haplotype and nucleotide diversity) at each site. Biomarker assays and genetic diversity were correlated with the chemical contaminants in bivalves using the Path-ComDim statistical model. Our results showed specific correlations between biochemical assays in the digestive glands with heavy metal contaminants, and between genetic diversity and organic pollution. Blocks of responses were analysed for correlations in order to develop standardized tools and guidelines that could improve our understanding of the short-term and long-term impact of contaminants on physiological parameters.