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Background: In different studies, the effectiveness of compassion-focused therapy and acceptance and commitment therapy on reducing psychological problems of patients with chronic disease has been investigated, but no research has compared the effectiveness of compassion-focused therapy and acceptance and commitment therapy on distress tolerance in women with Systemic lupus Erythematosus (SLE). Aims: The present research was aimed to compare the effectiveness of compassion-focused therapy and acceptance and commitment therapy on distress tolerance in women with SLE. Method: The current study was a semi-experimental research in which a pretest-posttest with control group design was used. The research population included all the women with SLE referring to the Rheumatology Clinic of Imam Khomeini Hospital and Tooba Clinic in Sari city, Iran, in the first half of 2019 who were156 individuals. Among this statistical population, a sample of 60 subjects were selected by purposeful sampling method who were assigned into two experiment groups and one control group by random assignment method. The research tool was Distress Tolerance Scale of Simons and Gaher (2005). The first experiment group received the compassion-focused therapy (Gilbert, 2010) and the second experiment group received the acceptance and commitment therapy (Hayes, Strosahl and Wilson, 2016) both in eight 120-minute sessions. For analyzing the data, the variance analysis with repeated measures and the Bonferroni ad hoc test were used. Results: Results indicated that compassion-focused therapy and acceptance and commitment therapy led to increase in distress tolerance and its components (tolerance, Absorption, Appraisal and regulation) at the end of the interventions and the follow-up stage. Also, compassion-focused therapy was more effective on increasing distress tolerance and its components than acceptance and commitment therapy (p< 0/01). Conclusions: The results of the present study confirmed the effectiveness of compassion-focused therapy and acceptance and commitment therapy on increasing distress tolerance among with SLE.