Objectives: The aim of this study was to evaluate the effect of fish oil supplementation on antenatal and postpartum depression score. Methods:This was a randomized, triple-blind, placebo-controlled trial. We enrolled 150 eligible pregnant women with Edinburgh postnatal depression scale (EPDS) score of less than 20, aged 18 to 35 from Feburary 2014 to April 2015 in Tabriz, Iran. Participants were randomly assigned to receive either 1000 mg of fish oil supplements or placebo from 16 -20 weeks of gestation to one month after giving birth. Participants completed the EPDS at baseline, 26 -30 weeks, 35 -37 weeks, and 30 -45 days after birth. Primary outcome measures were the mean depression score at 26 -30 weeks, 35-37 weeks, and postpartum period. The statistical analysis was intent-to-treat. Results:A total of 150 females were included, and no one was lost to follow up. There were significant differences between the two groups in the mean score of depression only at 35 -37 (adjusted mean difference = -1.4; [95% CI -2.6 to -0.25]). The mean score of depression during pregnancy and postpartum period significantly decreased within the fish oil group (P < 0.05). There were no significant differences between the two groups in terms of the baseline docosahexaenoic acid (DHA) and eicosapentaneoic acid (EPA) serum levels. Conclusions:Fish oil supplements significantly decreased the mean score of EPDS at weeks 35 to 37. It seems that females may benefit from daily fish oil supplements during pregnancy especially in countries with low intake of fish yet further studies are needed to confirm these results.