A total of 120 Oreochromis niloticus were collected randomly and seasonally. Fish were examined freshly from western lagoon (Berket El-Siadin) which is branch from Lake Temsah in Ismailia governorate .the result revealed that post mortem lesions in liver was in the form of  pale and enlargement in some cases, while in other cases showed variable degrees of congestion and hemorrhage spots. Spleen was dark in color and enlarged, kidneys appeared congested and the gall bladder was full and distended. The periodic difference of heavy metals  concentration based on the data of water samples gathered from the same lagoon showed the following manner as: summer > autumn >winter. The results revealed the presence of metals in the following order: Fe > Cu >Pb > Zn > Cd. The concentration of heavy metals in fish liver, gills and musculature were always higher than of the water, indicating the bioaccumulation. The highest concentration of heavy metals in water and fish tissue was associated with the lowest RBCs count, Hb, PCV, leukocytosis, hypoproteinemia and elevation in serum AST and ALT levels than normal. So, there is accumulating evidence that some heavy metals are immunosuppressive and fish may be more exposed to disease.