Background: Patients with the major depressive disorder have prominently been reported with subnormal omega-3 polyunsaturated fatty acids (PUFAs) levels, including importantly low eicosapentaenoic acid and docosahexaenoic acid in cell plasma and dietary intake. However, more randomized controlled trials are needed to support its importance in the management of depression. Objective: To explore the role of omega-3 polyunsaturated fatty acid in the management of the major depressive disorder. Materials and methods: Total 70 patients of aged 20 to 40 years old, who were already diagnosed with depression and taking antidepressant treatment, were selected at Department of Psychiatry and Behavioral Sciences, King Edward Medical University Lahore, and were assigned into 2 groups, i.e. intervention and control, by simple random lottery method. For 12 weeks, the intervention group was advised to take one omega-3 (300 mg EPA, eicosapentaenoic acid and 200 mg DHA docosahexaenoic acid), or placebo (500 mg corn oil) capsules once daily with a meal. Beck depression inventory (BDI) scale was used to assess the depression. Demographic information was collected using a structured questionnaire. SPSS version 20 was used for data analysis. Chi-square test was used to check the association between depression and risk factors. Paired t-test was applied to measure the mean difference before and after the intervention. Results: Statistically significant role of omega-3 PUFAs 15.46 ± 4.98 (p=0.000) was found. And mean was found insignificant in the placebo group as 2.32 ± 4.43 (p=0.007). Conclusion: It is concluded that omega-3 polyunsaturated fatty acid has a statistically obvious role in reducing depression as an add-on treatment with anti-depressants in the intervention group as compared to the placebo group.