Objective: The aim of this study was to evaluate the efficacy of acceptance and commitment therapy (ACT) in the reduction of disappointment, psychological distress, and psychasthenia among patients with systemic lupus erythematosus (SLE). Method: This quasi-experimental study was conducted on 24 females with lupus who referred to the Rheumatoid Disease Research Center (RDRC) of Ghaem hospital in Mashhad, Iran. This study had a pretest-posttest control group design. The participants were randomly assigned into 2 groups of experimental and control. The experimental group was treated with ACT. Data were collected using the Beck’s Hopelessness Scale, Kessler’s Psychological Distress Inventory, and Krupp’s Psychasthenia Inventory. Results: Mean age and mean duration of illness were 37.25±4.61 and 5.12±2.33 years, respectively. The mean disappointment score and psychological distress in the experimental group were lower compared to those in control group at the post experimental stage (P<0.001). Moreover, there was a significant difference between the experimental and control groups in the mean scores of psychasthenia in the posttest stage (P<0.001). Conclusion: According to the obtained results of this study, the enhancement of psychological flexibility based on ACT positively affected disappointment, psychological distress, and psychasthenia

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