Oxidative stress and inflammation are common manifestations of end-stage renal disease (ESRD) and major mediators of its cardiovascular and various other complications. Oxidative stress and inflammation are intimately interrelated as each can cause the other. The present study tested the hypothesis that antioxidant therapy may alleviate oxidative stress and thereby improve inflammation in ESRD patients. To test this hypothesis, we studied 37 hemodialysis patients of whom 20 (aged 53 ± 14 years) were treated with a combination of vitamin (V) E, 800 IU; VC, 250 mg; VB6, 100 mg; VB12, 250 μg; and folic acid, 10 mg daily for 8 weeks. The remaining 17 patients (aged 51 ± 15 years) received placebo. Predialysis levels of f-2 isoprostane (a marker of oxidative stress), C-reactive protein (CRP, a marker of inflammation), and interleukin (IL)-6 (a potent proinflammatory cytokine) were measured prior to and at 4 and 8 weeks after the onset of therapy. Diabetes was the cause of ESRD in 14 of the antioxidant-treated and 9 of the placebo-treated patients. Kt/V (1.56 ± 0.22 vs 1.61 ± 0.23), predialysis blood pressure (155 ± 79 vs 154 ± 8 mm Hg), hemoglobin (11.7 ± 1.3 vs 12.1 ± 1.2 g), and ferritin levels (217 ± 135 vs 301 ± 157 ng/mL) were similar among antioxidant- and placebo-treated groups at baseline and were virtually unchanged throughout the study period. Likewise, f-2 isoprostane, IL-6, and CRP concentrations remained unchanged and were unaffected by antioxidant or placebo administration. Moreover, no significant changes were observed in any clinical parameters. In conclusion, consumption of a high-dose antioxidant cocktail for 8 weeks failed to significantly change either the clinical or biochemical parameters or plasma markers of oxidative stress and inflammation in ESRD patients.