Concerning the hedonic valence, two pleasant odorants were evaluated as less pleasant by depressed SP600125 subjects before and 6 weeks of antidepressant treatment: vanillin and cinnamaldehyde. This result is in accordance with persistent olfactory anhedonia for everyday life odorants. Regarding the odor intensity, our results partly confirm that depressed subjects evaluated the unpleasant stimuli as more intense. Indeed, two concentration levels for unpleasant component were evaluated as significantly more intense by patients even after 6 weeks of antidepressant treatment. We replicate here previous findings, confirming the “olfactory negative alliesthesia” in depressed subjects at the quantitative level. In our sample, patients and controls were comparable when evaluating the odor intensity of pleasant stimuli, which was not observed previously. This difference may be explained by the difference in the type of used odorants, their intensity level and their emotional impact on the subjects. Moreover, our depressed group failed to discriminate correctly the three different concentration levels, both for pleasant and unpleasant stimuli. Likewise, this parameter did not improve after the treatment. The persistence of these olfactory alterations in clinically improved patients may have different explanations. First, the persistence of olfactory impairments despite euthymia could be due to the repetition of depressive event and the chronicity of this disease. Thus, we assume that the patients’ olfactory and cognitive abilities after 6 weeks of antidepressant treatment were not completely restored compared to healthy volunteers. Indeed, many authors have already observed that biological and cognitive markers of major depression are not improving after antidepressant treatment. For instance, some authors have shown that fluoxetine did not restore brain activity in mice. Besides, other authors have described the persistence of cognitive impairments in remitted patients after a MDE. In our study, we used a selective serotonine reuptake inhibitor with only weak affinity for dopamine transporters. Because of the major implication of dopamine in depression and in olfactory mechanisms, it is possible to show that this antidepressant treatment can’t normalize some cognitive impairments in clinically improved patients as olfactory ones. In addition, during the MDE and after clinical improvement. Our data also demonstrated that the depressed patients tended to perceive more the unpleasant compound compared to the controls. This observation suggests that the loss of appetite frequently described during MDE could be partly explained by this modification in olfactory perception, which is expressed as an “olfactory negative alliesthesia”. This is the first study to explore olfactory perception of complex odorant environment in clinically improved patients. In everyday life, subjects are confronted to complex odorant mixtures. This experiment is of great interest because it reflects more the reality of one patient’s olfactory environment. This innovative approach paves the way for future studies aiming at investigating olfactory alterations in neuropsychiatric disorders. The present study brings new evidence about olfactory impairments associated with MDE. Different olfactory impairments were tested as potential state or trait olfactory markers for MDE. Our results confirm the “olfactory anhedonia”, expressed by a decrease of hedonic score for high emotional odorant.