A eutrophic and metal-contaminated coastal system (Obidos lagoon, Portugal) was monitored combining water/sediment quality parameters and Carcinus maenas biomarkers (accumulated metals, oxidative stress and biotransformation responses). Two confined branches (Barrosa and Bom-Sucesso) were surveyed and compared with a reference area. Both crab genders from Barrosa exhibited activation of hepatopancreas CAT, GPx and GST, pointing out this area as the major impacted in the lagoon. Females captured at Barrosa were more vulnerable to peroxidative damage while only males showed decreased EROD activity, reinforcing gender specificities. In general, responses were not directly attributed to metals in hepatopancreas, as supported by Principal Component Analysis (PCA). However, higher metals (Ni, Cu, Cd) and nutrients levels registered in Barrosa water were associated with the observed oxidative stress responses by PCA. Despite the difficulty to establish cause-effect relationships due to the co-occurrence of various stressors and their interactions, the adopted integrated monitoring strategy appears to be promising.