Introduction This study aimed to evaluate the effectiveness of the “ well-being therapy" method on the clinical syndrome in patients with major depression as a randomized clinical trial. Materials and Methods This randomized clinical trial study was performed on patients with major depression who referred to the psychological clinic of Shamim, Bojnurd city in the period from November 2018 to February 2019 years. Participants eligible to enter the study were assigned to the intervention and control groups with a random block method. In the intervention group, Well-being therapy was performed in 8 sessions of 50 minutes and once a week, and the control group did not receive any treatment. Both groups were evaluated before and after the study and two months later by the Second Depression Beck Depression Inventory (BDI-II). Data were analyzed by T-test independent and generalized estimation equations (GEE) in STATA12 statistical. Results A total of 24 subjects had inclusion criteria in which 12 participants were randomly assigned to each group. Independent T-test results showed a significant difference between the mean depression scores of the groups after the study and the follow-up period (P-value <0. 05). The results of the GEE test showed that in the well-being group, the mean depression scores decreased 10. 90 rather than the control group (p-value <0. 0001). Conclusion The results of this study showed that well-being therapy can be effective in reducing depression in patients with major depression.