The invasive blue crab Portunus segnis, which was collected from two sites on the Gulf of Gabès, is the subject of this work. This study is based on demonstrating the accumulation capacity of P. segnis by measuring the concentrations of cadmium, zinc, lead, and copper in the gills and hepatopancreas. The enzymatic activities of catalase, glutathione-S-transferase, reduced glutathione, and lipid peroxidase were assessed in this region for the first time. The main results show that the metals have high bioaccumulation potentials in P. segnis tissues between different sites. The possible adaptation of P. segnis in the Gulf of Gabès and the variations in the studied biomarkers and metal concentrations at different sites confirm the usefulness of the invasive blue crab as a sentinel species.