Abstract: The present study was designed to investigate the biochemical toxicity and influence of antioxidant defense. Experiments were undertaken with different doses (100, 250, 500, 750 and 1000 ppm) of CuSO4-supplemented casein diet (CSCD) in commercial Quail. The following parameters were studied. (1) CuSO4 concentration in liver; (2) effect on body weight; (3) estimation of the serum levels of ALT, AST, alkaline phosphatase, uric acid, total proteins and blood glucose; (4) analysis of the plasma levels of total lipids, cholesterol, HDL and LDL and (5) estimation of malonaldehyde (MDA), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) levels in the plasma. The results demonstrated increase in the Cu contents of liver and caused significant loss of body weight. Although the treatment enhanced antioxidant defense enzymes (SOD and GSH-PX), there was no reversal observed in the induced biochemical toxicity, including the increase of MDA. This study revealed that pro-oxidant activity of CuSO4 superceded the endogenous antioxidant defense, which might be a major factor in the pathogenesis of several drastic diseases, both in birds and humans. The beneficial effects of Cu may be utilized by reducing the levels of supplementation. Further experiments are suggested on characterization of dose-response relationship by mathematical modeling. This might require the use of a sufficient number of lower doses to determine a threshold dose below which there would be no toxicity.