Abstract INTRODUCTION: The relationship between ω -۳ fatty acids and surrogate circulating markers of cardiovascular disease (CVD) risk, especially in healthy individuals remains to be determined. We investigated the effects of Eicosapentaenoic acid (EPA) supplementation, with or without vitamin E, on serum lipid profile, C-reactive protein (CRP), blood pressure (BP) and total antioxidant capacity in a sample of male athletes. methods: This randomized double blind placebo-controlled clinical trial was conducted in ۲۰۰۶ on ۳۴ apparently healthy, well-trained male basketball players, aged ۱۷-۳۵ years, . Venous blood samples were obtained between ۵:۰۰ and ۶:۰۰ p.m., after exercising for ۲ hours, at the baseline and after intervention. Participants received ۲ g EPA and/or ۴۰۰ IU vitamin E and/or placebo depending on their groups. For ۶ weeks, eight subjects received an EPA supplement with vitamin E (group ۱), nine subjects received an EPA supplement with vitamin E placebo (group ۲), nine subjects received an EPA supplement placebo and vitamin E (group ۳), and eight subjects received an EPA supplement placebo and vitamin E placebo (group ۴). results: Significant decreases were documented in the serum levels of total cholesterol (TC), triglycerides ( TG), LDL-C and CRP in group۱ (p<۰.۰۱), in TC, TG, LDL-C, CRP, and BP in group ۲ (p<۰.۰۱), and significant increase in total antioxidant capacity in group ۳ (P<۰.۰۵). No significant difference was found in LDL between groups ۱ and ۴ (P<۰.۰۵), and in total antioxidant capacity between groups ۲ and ۳ (p<۰.۰۰۱) and groups ۳ and ۴ (p<۰.۰۰۱), and in CRP level between groups ۲ and ۳ (P<۰.۰۵). There were no significant differences in TC, TG, HDL-C and BP between the groups after ۶ weeks of intervention. CONCLUSIONS: Six weeks of EPA+ vitamin E supplementation improved the lipid profile and reduced the CRP level, whereas six weeks of EPA supplementation without vitamin E improved the lipid profile, but increased CRP and BP. Six weeks of vitamin E supplementation alone increased total plasma antioxidant capacity. Keywords: Eicosapentaenoic acid, vitamin E, lipid, antioxidant, inflammation, healthy men, exercise.