Abstract: The effect of exposure to petroleum contaminated diet on the blood antioxidant defence system, lipid peroxidation and lipid profile as well as possible protective roles of vitamins E and C were studied in rabbits. Oxidative stress induction by crude oil was indicated by significantly (P<0.05) increased lipid peroxidation and a non-significant decrease in superoxide dismutase and catalase activities. A similar pattern was also detected in the lipid profile: total cholesterol and LDL-cholesterol insignificantly increased while HDL-cholesterol and triglyceride significantly decreased relative to rabbits fed normal diet. The reciprocal relationship between HDL-cholesterol and LDL-cholesterol in addition to compromised antioxidant enzymes could predispose exposed animals to coronary heart disease. However, pre-treatment of the diet with vitamins C and E exhibited a protective role on the toxic effect of crude oil on lipid profile, lipid peroxidation as well as antioxidant enzymes. The order of protection was vitamins E + C > vitamin E > vitamin C. These observations seemed to suggest that the protective role of vitamins C and E is synergistic. The protective role of the vitamins is probably time-dependent as significant (P<0.05) restoration of lipid profile as well as antioxidant enzymes activities to control values was effected after four weeks of exposure. It is therefore suggested that toxic effect of petroleum may be reduced by dietary supplementation of vitamins C and E.