During endurance exercise, oxygen consumption by the skeletal muscle can increase 100–200 times. We previously found that during an ultramarathon race (50 km, forest trail through hilly terrain) compared with a day of rest, vitamin E disappeared faster (as measured using 2H-labelled α-tocopherol) and lipid peroxidation increased. Therefore, we hypothesized that prior supplementation with antioxidants (vitamins E and C) would decrease oxidative stress during distance running and, therefore, decrease lipid peroxidation and inflammation, decreaseDNA damage, decrease muscle damage and/or improve recovery. To test these hypotheses, we carried out a randomized, double-blind study in runners (n 11 females, 11 males) who were participants in an annual ultramarathon race. We found that supplementation with both vitamins E and C only prevented increases in lipid peroxidation, but had no apparent effect on DNA damage, inflammation or muscle damage. These results suggest that the mechanism of oxidative damage is operating independently of the inflammatory and muscle damage responses.