Background: Coronary Artery Disease (CAD) is one of the largest causes of mortality worldwide. Clopidogrel, antiplatelet drug, has been widely used for management of CAD. The current study aimed to investigate the effect of clopidogrel on the oxidative stress in CAD patients. Methods: One hundred CAD patients, who were followed-up for 5 days after receiving clopidogrel, and 50 healthy volunteers were included in this study. Parameters include catalase (CAT), total antioxidant capacity (TAC), total oxidant capacity (TOC), total protein, albumin, and globulins were determined before and after treatment with clopidogrel. Results: CAT, TAC, and Tp were significantly decreased (P<0.0001) in CAD patients compared to healthy control and the levels of these parameters were returned to increase after receiving clopidogrel. However, TOC level was markedly increased (P<0.0001) in CAD patients and returned to decrease after treating with clopidogrel. Receiver operating characteristic curve showed that CAT gave a higher sensitivity (68-73%) and specificity (72%) as an indicator for monitoring of CAD progression. Conclusion: CAT activity and TAC were significantly increased as a response of receiving clopidogrel which is helpful to reduce the risk of CAD through scavenging of oxidants formation. These results also present CAT as a predictor variable of clopidogrel action.