This study discusses the efecfts of heavy metal contamination in aquaculture ponds on Oreochromis niloticus (Tilapia fish). The effects of sub-lethal exposure to cadmium chloride and lead acetate on oxidative stress biomarkers (lipid peroxidation product) and antioxidant biomarkers (reduced glutathione) were investigated in O. niloticus. The determination of GSH was dependent on the precipitation of protein using a tungstate. Sulfuric acid solution and the formation of yellow color after reaction with 5, 5` dithiobis-25-nitrobenzoic acid (DNTB) was measured at wave length 412 nm. There was a significant decrease in reduced glutathione (GSH) after exposure to different doses of cadmium chloride and lead acetate and a significant increase in lipid peroxidation product (LPO) after exposure to different doses of cadmium chloride and lead acetate. The investigation indicates that the cadmium chloride and lead acetate are elevating the level of lipid peroxidation which are toxic in Tilapia fish.