PURPOSE: This study investigated the effects of 750 mg of soybean-derived phosphatidylserine (S-PtdSer), administered daily for 7 d prior to a bout of eccentric exercise and for 2d following exercise, on delayed onset of muscle soreness and markers of muscle damage, inflammation, and oxidative stress that followed prolonged downhill running. METHODS: Following preliminary testing and a familiarization session, eight recreationally active males repeated an individualized downhill run at -16.5% for 51.0 +/- 1.5 min at 8.7 +/- 0.3 km x h(-1) on four occasions (trials 1-4). Trials 1 and 37 were presupplementation control trials. After trials 1 and 3 the subjects received, in a double-blind and crossover fashion, either S-PtdSer or a glucose polymer placebo. Trials 2 and 3 were separated by a 4-wk washout period. Venous blood, perceived soreness ratings, and feeling states were assessed prior to exercise, after exercise, and at 24 and 48 h after exercise during each trial. RESULTS: Downhill running led to elevations in perceived soreness (P < 0.05), creatine kinase activities (P < 0.001), myoglobin concentrations (P < 0.001), interleukin-6 (IL-6) concentrations (P < 0.001), and lipid hydroperoxide concentrations (P < 0.01). However, supplementation did not significantly attenuate these responses. CONCLUSION: These results suggest that supplementation with 750 mg x d(-1) S-PtdSer for 10 d does not afford additional protection against delayed onset of muscle soreness and markers of muscle damage, inflammation, and oxidative stress that follow prolonged downhill running.