Oxidative stress plays an important role in the pathogenesis of cardiovascular disease (CVD). Growing evidence suggest that antioxidant vitamins might reduce the risk of disease outcomes by their ability to scavenge free radicals. The aim of the present study was to evaluate the supplementation of vitamins E and C on oxidant and antioxidant status in CVD patients. We conducted a case-control study with vitamin E (400 IU/d) and vitamin C (500 mg/d) supplementation in 40 CVD patients for 2 mo. Antioxidant (enzymatic and non-enzymatic) and oxidant status were analyzed pre and post supplementation. In the initial stage the activity of both enzymatic and non-enzymatic antioxidants were lower, while the malondialdehyde (MDA) level was elevated (p<0.0001). After intervention, a significant increase in superoxide dismutase (SOD) activity (61.7%), glutathione peroxidase (GPx) activity (59.3%), the levels of vitamin E (83.7%), C (145.3%), total antioxidant capacity (TAC) (62.8%) and a significant decrease in MDA (40%) value were observed (p<0.0001). There was a significant negative correlation between MDA and TAC. The results suggest that supplementation with a combination of vitamins E and C reduced lipid peroxidation and strengthened the antioxidant defense system. Hence, there will be beneficial effects on the heart by reducing oxidative stress in CVD patients.