Cigarette smoke is a major risk factor for both coronary heart disease and peripheral vascular disease and has been reported to contain many oxidizing agents that lead to generation of free radicals. In this study, we investigated the levels of lipid peroxides (LPO) and antioxidant vitamins (C and E), total thiol content (t-SH), the activities of superoxide dismutase (SOD), glutathione S-transferase (GST) and glutathione peroxidase (GPx) in the platelet-rich plasma (PRP) and plasma of 50 smokers and 30 non-smokers. Total cholesterol (TC), low density-cholesterol (LDL-C), triglyceride (TG) and phospholipid (PL) levels of the plasma were significantly higher (p < 0.001) and high density-cholesterol (HDL-C) levels were significantly lower in smokers (p < 0.001) when compared with non-smokers. In plasma and PRP, LPO levels, GST and SOD activities were found to be increased (p < 0.001) in smokers, whereas GPx activity, vitamin C levels and t-SH content were found to be decreased. On the other hand, the levels of vitamin E was unchanged in plasma and PRP. The relationships between plasma levels of lipids, LPO and antioxidant systems were also investigated in both groups. A strong positive correlation was found between TC and Vit E (r = 0.5575; p < 0.001), LPO and PL (r = 0.4270; p < 0.01), LPO and GST (r = 0.3770; p < 0.01) and t-SH and GPx (r = 0.3781; p < 0.01) in smokers. These findings reveal a disturbance of oxidant-antioxidant balance by free radicals present in cigarette smoke, which may cause reduction in platelet hyperreactivity and endothelial dysfunction in smokers.