In a large, prospective, 8-week open study of 721 outpatients receiving agomelatine treatment for a current major depressive episode (MDE), morningness-eveningness (Composite Scale of Morningness) was assessed before and after treatment to investigate possible changes in morningness-eveningness after treatment and evaluate whether morningness-eveningness at baseline predicted treatment response. A change towards morningness was observed after treatment. This change was greater in responders than non-responders. Moreover, being a morning type at baseline was an independent predictor of response to treatment. Once thought to be a trait variable, morningness-eveningness is a potential treatment target that should be systematically assessed in MDE patients.