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Background: One of the most prevalent mood disorders is depression which comprising of symptoms like persistent sadness or low mood, loss of interest or pleasure and fatigue or low energy at least one of these, most days, most of the time for at least 2 weeks. Psychosocial or social is one of the important domains of cognition affected by depression. With the phenomenon of depression, there is often a shift in one’s social behaviour. Objective: This study aimed to compare the effect of fluoxetine, venlafaxine, and mirtazapine on psychosocial functioning in patients with major depressive disorders. Material & Methods: 30 patients of age between 18-69 years of either sex were randomly allocated to receive either fluoxetine (20-40mg), venlafaxine (75-150mg) or mirtazapine (15-30mg). Patients were diagnosed by DSM IV- RC. The patients were clinically assessed by using ABC-Hamilton Depression Rating Scale. The evaluation of patient social motivation and behaviour in depression was done by using Social Adaptation Self-Evaluation Scale (SASS) at the time of enrolment and then at the end of the sixth and twelfth treatment weeks. Results: In Group fluoxetine, scores of SASSS on the day of enrolment, 6th and 12th week were 26.76 ± 4.52, 39.92 ± 5.00, and 51.15 ± 4.78 respectively. Similarly, in group venlafaxine scores of SASSS on the day of enrolment, 6th and 12th week were 29.80 ± 9.00, 39.42 ± 10.21, and 51.5 ± 4.75 respectively. In Group mirtazapine, scores of SASSS on the day of enrolment, 6th and 12th week were 29.80 ± 9.00, 39.42 ± 10.21, and 51.5 ± 4.75 respectively. Our results showed that in all three groups there is improvement in social behaviour after the 6th and 12th week from the baseline scores. At the end of the sixth and twelfth weeks of treatment, however, there was no statistically significant difference between the three groups on an intragroup basis. Conclusion: The SASS total score improved with a varying degree with patient status and is sensitive to active-treatment effect., http://impactfactor.org/PDF/IJTPR/12/IJTPR,Vol12,Issue12,Article16.pdf