Bivalves can accumulate toxicants such as heavy metals in their tissues, for this reason, they are considered as good bio-indicators for water quality. The risk is increased due to eating these clams raw or lightly cooked. This study aims to determine the concentration of some selected metals (Cu, Zn, Mn, Cd, and Pb) in the soft tissue of Ruditapes decussatus collected in the summer of 2017, from three locations at Alexandrian coasts, Egypt, Abo Quir, (loc.#1), Sedi Beshr (loc.#2) and (loc.#3), El-Max)  and to find out whether pollution alters the clam physiological functions or not. The present data showed that the highest mean value of salinity was reported in water samples collected from Abo Quir (loc.#1) and the highest level of dissolved oxygen was reported in water samples collected from Sedi Beshr (loc.#2). The present results showed that the studied heavy metals concentrations are highly significant in samples of water and soft tissue of Ruditapes decussatus collocated from Abo Quir bay. From the above-cited results, it is concluded that loc.#1(Abo Quir bay) represents the most polluted site in the present study. Statistical analysis showed a significant increase of MDA and a significant decrease of SOD and GPx in the soft tissue of Ruditapes decussatus collected from Abo-Quir Bay (loc.#1). There was a highly significant difference between the concentration of MDA, SOD, and GPx in the tissue of clams collected from the three locations (p < 0.001). The correlation coefficient of heavy metals in tissue, heavy metals in water, and oxidative stress biomarkers showed that the concentration of MDA in the tissue of calm collected from Abo Quir Bay (loc.#1), Sedi Beshr (loc.#2), and El-Max (loc.# 3) were positively correlated with the mean activity level of SOD and the concentration of SOD in the clam's tissue collected from Abo Quir Bay (loc.#1) and  Sedi Beshr (loc.#2) were negatively correlated with the activity level of GPx. The present work also showed that the correlations between different heavy metals in the tissues of R. decussatus collected from three locations indicated that different rates and mechanisms of metal accumulation were taking place.