The aim of this study was to investigate the effect of phosphatidylserine (PS) on cognition and cortical activity after mental stress. After familiarization, 16 healthy subjects completed cognitive tasks after induced stress in a test-re-test design (T1 and T2). Directly after T1, subjects were assigned double-blind to either PS or placebo groups followed by T2 after 42 days. At T1 and T2, cortical activity was measured at baseline and immediately after stress with cognitive tasks using electro-encephalography (EEG). EEG was recorded at 17 electrode positions and fast Fourier transforms (FFT) determined power at Theta, Alpha-1, Alpha-2, Beta-1 and Beta-2. Statistics were calculated using ANOVA (group x trial x time). The main finding of the study was that chronic supplementation of phosphatidylserine significantly decreases Beta-1 power in right hemispheric frontal brain regions (F8; P < 0.05) before and after induced stress. The results for Beta-1 power in the PS group were connected to a more relaxed state compared to the controls.