This study is concerned with the contamination of heavy metals and its effect on biochemical parameters and enzyme activity of the Nile tilapia collected from three fish farms. For this reason, the physical and chemical parameters of farms water were examined. Also, heavy metals (Zn, Cd, Pb, Fe, and Cu) were measured in water, fish blood, and sediment collected from the farms under study. The results of pH in the three farms EL-Galini, Locanda, and EL-Bats were 7.95, 8.03, and 8.06, respectively where, dissolved oxygen were 5.9, 7.2, and 6.0 (mg/l). The values of heavy metals in water showed relative variation Fe>Zn>Cu>Pb>Cd in all three different farms. For sediment EL Galini farm have the highest value for all the examined heavy metals followed by Locanda and EL-Bats farm. The results showed a significant increase in levels of (Random blood sugar), and (Alkaline Phosphatase) with P-value 0.004, 0.002 respectively in both Locanda and EL-Bats farms when compared with EL Galini farm. Also, there was a significant decrease in levels of creatinine, (Creatinine Kinase) and (Aspartate Transferase) with P-value 0.02 and 0.05 for creatinine, <0.001 and <0.001 for CK and <0.001 and <0.001 for AST, respectively in both Locanda and EL-Bats farms when compared with EL Galini farm.