The date mussels (Lithophaga lithophaga) are rock-boring bivalve molluscs that are generally used as bio-indicators for pollution. They can accumulate pollutants in their tissues, due to their filter feeding behaviour. Therefore, the current study aimed to use the date mussels to evaluate the heavy metal pollution in three coastal areas of Alexandria (Abo Qir, Alasafra, and Miami) during the four seasons to determine the most polluted area. The current study also aimed to evaluate the health status and disease burden of the date mussels collected from the most polluted area according to the World Organisation for Animal Health (OIE) manual. The results indicated that Pb, Cd, and Cu increased significantly in seawater of Abo Qir area during summer, and was correlated with their accumulation in the mussel tissues. As a consequence of pollution, a significant decrease in the amount of dissolved oxygen was observed in the seawater of Abo Qir area during summer. The pathological examination of samples from Abo Qir area using OIE manual showed that the mussels had signs of weakness from the outer shell examination as gaping, fragility, discolouration, and fouling. Moreover, infection with ciliates was observed in the date mussel tissues collected from the most polluted area. Interestingly, abnormal case of disseminated neoplasia or sarcoma also appeared under the effect of pollution. In conclusion, Abo Qir is the most polluted area with low dissolved oxygen concentration during summer. Moreover, accumulation of heavy metals in the soft parts of the date mussels could increase their disease susceptibility.