To test the effects of combined coenzyme Q10 (Q10) and d-alpha-tocopheryl acetate supplementation on exercise-induced oxidative stress and muscular damage we conducted a double-blind study in 37 moderately trained male marathon runners. These were randomly allocated to receive either an antioxidant cocktail: 90 mg of Q10 and 13.5 mg of d-alpha-tocopheryl acetate daily (18 men) or placebo (19 men) for three weeks before a marathon (42km) run. Just before the run, plasma Q10 was 282% (p < 0.0001) and plasma vitamin E 16% (p < 0.007) higher in the supplemented group, than in the placebo group. Also the proportion of plasma ubiquinol of total Q10, an indication of plasma redox status in vivo, was significantly higher in the supplemented group. Furthermore, the susceptibility of the VLDL + LDL fraction, to copper-induced oxidation, was significantly reduced in the supplemented group, compared to the placebo group. The exercise increased lipid peroxidation significantly in both study groups, as assessed by the elevated proportion LDL of LDL and the increased susceptibility of lipoproteins to copper induced oxidation. However, the supplementation had no effect on lipid peroxidation or on the muscular damage (increase in serum creatine kinase activity or in plasma lactate levels) induced by exhaustive exercise. Plasma ascorbate, Q10, whole blood glutathione and serum uric acid concentrations increased during the exercise, elevating significantly the TRAP value of plasma by 10.3% and the proportion of plasma ubiquinol of total Q10 by 4.9%. These results suggest that even though exercise increases plasma lipid peroxidation, it also elevates the antioxidative capacity of plasma, as assessed by the increased plasma TRAP and the proportion of Q10H2 of total Q10. However, prior supplementation with small doses of Q10 and d-alpha-tocopheryl acetate neither attenuates the oxidation of lipoproteins nor muscular damage induced by exhaustive exercise such as encountered in a marathon run.