Increasing clinical reports show that major depression is characterized by pronounced olfactory deficits, yet the underlying mechanisms remain unknown. In this work, we used an endocrine model of depression to study whether hypothalamic-pituitary-adrenal axis perturbation could be sufficient to provoke olfactory impairments. We found that chronic corticosterone not only induces marked deficits in olfactory acuity, fine discrimination and olfactory memory, but also significantly decreases bulbar and hippocampal neurogenesis. Importantly, the antidepressant fluoxetine restores both adult neurogenesis and depressive states, and improves most olfactory functions. Our data reveal that impairment of hypothalamic-pituitary-adrenal axis during depression can lead to olfactory deficits and that the neurogenic effects of selective serotonin reuptake inhibitor antidepressants can successfully restore certain olfactory functions.