The nasal cycle is a phenomenon whereby alterations in airflow alternate between left and right nostrils. During a nostril’s decongested – or dominant – state, the contralateral nostril is congested, or non-dominant. Intranasal oxytocin may elicit anxiolytic effects. To date, no study has investigated whether there is an optimal nasal pathway for oxytocin’s effects. Forty-four female adolescents aged 16 to 17 years were included in this exploratory study investigating effects of nasal dominance on intranasal oxytocin delivery. We show that intranasal oxytocin significantly reduces stress relative to placebo (<jats:italic>p</jats:italic> = 0.012, ηp<jats:sup>2</jats:sup> = 0.145) and greater stress reduction occurs when oxytocin is delivered to the dominant, rather than non-dominant, nostril (<jats:italic>p</jats:italic> = 0.034, ηp<jats:sup>2</jats:sup> = 0.113). We postulate that oxytocin administration may reduce stress and be most effective in the context of anxiolysis when administered to the dominant nostril. Further research investigating whether other intranasal psychotropic drugs have nostril-specific effects might benefit clinical practice.