Objective: The efficacy of antidepressants in the treatment of mild-to-moderate postpartum depression and the possible advantage of the combination of an antidepressant and psychotherapy have not been adequately studied. We hypothesized that psychotherapy and concurrent antidepressant treatment would be more effective than psychotherapy alone in the treatment of postpartum depression. Method: Women diagnosed with mild-to-moderate severity postpartum depression according to DSM-IV-TR criteria were enrolled in an 8-week, randomized, doubleblind, placebo-controlled study. Participants received 12 sessions of focused brief dynamic psychotherapy (BDP) concurrently with 8-week sertraline or placebo treatment, followed by a 4-week open phase. Primary outcomes were depression scores measured by the Montgomery-Asberg Depression Rating Scale (MADRS) and remission rates. The study was conducted in a referral center from May 2008 to September 2010. Results: Forty of 42 women randomized into the study entered the intent-to-treat analysis. A significant time effect for the MADRS was observed (F4,35 = 21.3, P < .0001); however, no time-by-group effect was found for any outcome measure. Response rates were 70% and 55% for the drug and placebo groups, respectively, and remission rates were 65% and 50%, respectively, with no significant difference between groups. Conclusion: While both treatment groups improved significantly, the results of the present study did not demonstrate a significant benefit for sertraline over placebo as an add-on treatment to focused BDP in mild-to-moderate postpartum depression. Because of the study's small sample, the results cannot be viewed as definitive, and a much larger study is needed to confirm these results. Furthermore, the promising potential of focused BDP as an intervention in this population should be studied under controlled conditions. Trial Registration: clinicaltrials.gov Identifier: NCT01028482.