The objective of this study is to evaluate the effects of bupropion as an add-on therapy to selective serotonin reuptake inhibitor (SSRI) on patients of major depressive disorder with partial response. This prospective, randomized, controlled and single-blind study was conducted in sixty patients suffering from major depressive disorder as per Diagnostic and Statistical Manual (DSM)-IV TR criteria, who were having Hamilton depression rating scale (HDRS) score ≥16 after 4 weeks of treatment with SSRIs. Group A received SSRI plus placebo and group B received SSRI plus bupropion. Evaluation was performed based on changes in HDRS score, Montgomery and Asberg depression rating scale (MADRS), Amritsar depressive inventory (ADI) and spontaneously reported adverse effects. There was a significant decrease in the HDRS, MADRS and ADI scores as compared to baseline in both groups. However, the mean decrease in depression score was more in group B than in group A. The percentage decrease of remitters was also significantly more in group B (60% as per HDRS score and 63% as per MADRS score), as compared to group A (24% as per HDRS score and 27% as per MADRS score) (p < 0.05), at the end of treatment. In conclusion, bupropion add-on can act as augmenting agent in patients of depression with partial response to SSRIs.