Odor deprivation leads to anatomical and neurochemical changes in the olfactory system, but its effect on human olfaction has not been systematically explored. The present randomized, controlled study aimed to investigate whether odor deprivation by different methods can affect olfactory function in humans. In the present study, sixty-one healthy participants were randomly assigned into three groups: a nasal device group (wearing an intranasal silicone air diversion system for 6–8 h daily), a mask group (wearing a filtering face piece for 6–8 h daily) and a control group (no special instructions in terms of wearing masks). Before and immediately after a 14-day study phase, all participants underwent assessments of olfactory function, nasal patency and well-being. Following the 2-week observation period, the nasal device group exhibited significantly reduced TDI scores (with especially pronounced reductions for odor threshold scores), and the mask group exhibited a minor increase in odor identification scores compared with the control group. The change in well-being scores was positively associated with changes in odor identification and TDI scores. Olfactory deprivation using an intranasal silicone air diversion device is associated with olfactory impairment (especially for odor thresholds). Highlighting the exposure-driven plasticity of the olfactory system, it may serve as a possible model of hyposmia in future studies. In addition, it may also prove useful in patients with parosmia, possibly reducing the burden of unpleasant odorous sensations.