BACKGROUND: Previous research has indicated that phosphatidylserine (PS) supplementation has the potential to attenuate the serum cortisol response to acute exercise stress. Equivocal findings suggest that this effect might be dose dependent. This study aimed to examine the influence of short-term supplementation with a moderate dose of PS (600 mg per day) on plasma concentrations of cortisol, lactate, growth hormone and testosterone before, during, and following moderate intensity exercise in healthy males. METHODS: 10 healthy male subjects participated in the study. Each subject was assigned to ingest 600 mg PS or placebo per day for 10 days using a double-blind, placebo-controlled, crossover design. Serial venous blood samples were taken at rest, after a 15 minute moderate intensity exercise protocol on a cycle ergometer that consisted of five 3-minute incremental stages beginning at 65% and ending at 85% VO2 max, and during a 65 minute passive recovery. Plasma samples were assessed for cortisol, growth hormone, testosterone, lactate and testosterone to cortisol ratio for treatment (PS or placebo). RESULTS: Mean peak cortisol concentrations and area under the curve (AUC) were lower following PS (39 +/- 1% and 35 +/- 0%, respectively) when compared to placebo (p < 0.05). PS increased AUC for testosterone to cortisol ratio (184 +/- 5%) when compared to placebo (p < 0.05). PS and placebo supplementation had no effect on lactate or growth hormone levels. CONCLUSION: The findings suggest that PS is an effective supplement for combating exercise-induced stress and preventing the physiological deterioration that can accompany too much exercise. PS supplementation promotes a desired hormonal status for athletes by blunting increases in cortisol levels.