Sensory gating, a viable function of the brain, is an adaptive mechanism to prevent overstimulation of nervous system. The aim of this study was to examine the effect of homobaric pure (i.e. 100%) oxygen on the human brain at different periods of inhalation. EEG was recorded while an auditory paired-click sensory gating test was conducted during 4 study periods: before inhalation of pure oxygen (Before), inhalation of 100% oxygen (air in control group) for 20 min (Oxy20) and 50 min (Oxy50), 30 min after oxygen (air in control group) inhalation (After). Each of the auditory stimuli elicited 4 clear peaks at 20, 39, 55 and 100 ms in ERPs, demonstrating that sensory gating is a multi-stage process. Comparing the S1-S2 differences of field potentials between two groups, significant experimental effects (P < 0.05-0.01) were shown at Oxy50 and After periods mainly at the 20 and 100 ms peak in ERPs. Pure oxygen was experimentally shown, for the first time, to affect the human brain activation, at the beginning of early P20 sensory cortical activation and late N100 auditory perception. The effect found in this study shall encourage further investigation on the oxygen treatment in human brain.