The present study aims to describe the effect of heavy metals: copper, manganese, iron and zinc on the water quality of El-Bagouria Canal at Kafr El-Zayat region, El-Gharbiah Governorate. Seasonal variations of physico-chemical parameters were studied during the period from summer, 2013 to spring, 2014. Also, to study their effects on the different organs of the commercial fish species; Nile tilapia, Oreochromis niloticus by studying some of biochemical parameters of this fish species (total protein, total lipids, total carbohydrates, ASAT and ALAT) during the study period.Results revealed that, heavy metals in the water showed seasonal variations. Also, data exhibited the highest values of heavy metals in the different organs of O. niloticus were recorded during winter in the liver and kidney and the lowest were observed in the muscles. Biochemical analysis indicated devastating effects, especially enzymes activities, in the metabolic organs. Statistical analysis using analysis of variance (ANOVA, at p<0.05) based on data represent the measured values of heavy metals in the different organs of O. niloticus during the different seasons. One way analysis proved that, there were highly significant differences between the metals and between the different seasons also between different organs. On the other hand, two ways of ANOVA provided highly significant differences between organs and metals at the same seasons. While, non-significant differences were detected at the interactions between seasons and organs at the same metals and between seasons and metals at the same organs. One way analysis for biochemical parameters in the different organs of O. niloticus during the different seasons proved that, there were highly significant differences between the parameters. Meanwhile, there were significant differences between the different seasons and between target organs. Moreover, two ways of ANOVA provided highly significant differences between organs and parameters at the same seasons. While, non-significant differences were found at the interactions between seasons and organs at the same parameters and between seasons and parameters at the same organs.