Heavy metal pollution may affect the aquatic organisms at the cellular level through the changing production of mRNA and proteins. To prove the extent of pollution in the study area; seven heavy metals: Zn, Cu, Cd, Pb, Fe, Ni, and Mn were measured using atomic absorption spectrophotometer in Rhabdosargus haffara (haffara seabream) fish liver, muscle, and gills tissues collected from northern of Suez Gulf in Egypt during winter and summer seasons. The field study area was divided according to the degree of heavy metal pollution in less and highly polluted areas. Elevated values of most studied metals concentrations were detected in fish tissues belong to the high polluted sites as compared to the less polluted sites. A study was performed between high and less polluted areas samples; to evaluate the effect of heavy metal pollution on Cytochrome c oxidase mRNA expression and alkaline phosphatase enzymatic activity in fish liver tissue. Using qRT- PCR, evidence of an increase in Cytochrome c oxidase in fish livers was detected in the highly polluted areas samples than those from less polluted. Relative quantitation of COX-1 was significantly highly expressed in liver tissue sampled from high polluted sources in response to heavy metal pollution as compared to less polluted sources for mRNA. Moreover, there was a high significant difference between winter and summer seasons in high polluted study areas than less polluted source samples