Background: The main drains at Fayoum governorate, El-Bats and El-Wadi loaded by salts and heavy metals as a result of the huge amount of the agricultural, waste municipal and industrial efflluents discharged.. Aim: The present investigation aims to determine     the effect of water quality including heavy metals (zinc, copper, lead and cadmium) on hematological changes of the Nile catfish; Clarias gariepinus collected from a branch of the river Nile (El-Lahon canal) and two main drains (El-Bats and El-Wadi) at Fayoum governorate. Materials and methods: water and fish samples collected from the two main drains and the branch of the river Nile at Fayoum governorate to follow the effect of water deterioration and heavy metals bioaccumulation on fish blood parameters. Results: Highly significant increase in values of ammonia, nitrite, heavy metals (Cu, Zn, Pb and Cd) and  a decrease in dissolved oxygen content in water samples collected from the main drains (El-Bats and El-Wadi) in comparision with that of samples collected from the branch of the river Nile. Moreover, bioaccumulation of the studied heavy metals in the main vital organs , gills , liver , kidney and muscles of Clarias gariepinus collected from the main drains at El-Fayoum governorate is accompanied by a significant decrease in RBCs , Hb content and PCV values but significant increase in MCV , MCH and MCHC WBCs of fish collected from El-Fayoum drainage canals (El-Bats and El-Wadi) than that of fish collected from the river Nile branch , El-Lahon that showed more or less normal values. Conclusion: Generally, the results highlights on the importance of taking action through the political authorities towards quality of the drainage water resources that fed fish farms by law and its fauna that could play        a role as a main source of protein for human beings.