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Background and Objectives: Rheumatoid arthritis is one of the most common diseases of the immune system which is increasing rapidly. The results of the recent literature review confirm the roles of stress and psychosocial stressors on physiological mechanisms, such as psychoneuroimmunology, as causal factors leading to the development of rheumatoid arthritis. Considering the effectiveness of psychological problems in the development of this disease, the present study was conducted to compare the effectiveness of coping therapy and cognitive-behavioral therapy in cognitive immunity and psychological well-being indicators of patients with rheumatoid arthritis referring to Imam Khomeini Hospital, Tehran, Iran. Methods: This was a quasi-experimental study with a pretest-posttest control group design. In the present study, the effectiveness of two independent variables (i.e., coping therapy and cognition-behavioral therapy) on dependent variables (i.e., immune-cognitive and psychological well-being indicators) was examined. The statistical population consisted of patients with rheumatoid arthritis referring to Imam Khomeini Hospital from March-August in 2019. The final sample (n=60) was selected by the purposive sampling method and the subjects were randomized into two groups of experimental and control (n=20 each). Subsequently, the experimental group was subjected to coping therapy and cognitive-behavioral therapy interventions. The instruments used in the present study included Psychological Welfare Scale, C-reactive protein (CRP) immunological indicators test, and erythrocyte sedimentation rate (ESR) test. The collected data were analyzed using the analysis of covariance model. Results: The results of the analysis of covariance model were indicative of a p-value of < 0.05 as significant. Moreover, it was found out that the effectiveness of coping therapy and cognitive-behavioral therapy on CRP, ESR, psychological well-being was significant (P