Abstract Objective Nitrous oxide (N2O) may elicit antidepressant effects after its elimination from the brain. We sought to investigate whether N2O trigger slow-wave oscillations in electroencephalogram (EEG) after it´s administration, as we have recently seen in animal studies. Methods Twenty healthy male participants were randomly allocated to receive 50% N2O either continuously for 20 minutes (continuous group) or in two 10-minute inhalations (repeated group) with EEG recording. The subjective effects of N2O were studied with questionnaires. Results Fourteen participants completed the study (N=7/group). Overall group-level responses to N2O on EEG were variable, and no difference in delta-theta range was observed. A rebound increase in slow wave bands was seen in spectrograms (Fp2 electrode) in a few participants, more markedly after the second 10-minute exposure to N2O. Gamma oscillations enhanced during N2O administration along with reductions in alpha and low beta band activity. Conclusions Short exposure to N2O elicited slow-wave EEG oscillations during rebound phase only in small subset of participants. Significance This study reveals high individual variability in EEG responses to short exposure of 50% N2O. Hence, the ability of N2O to trigger rebound slow-wave EEG activity may require tailored dosing regimen for each individual.