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Background and Aim Fibromyalgia syndrome is a chronic disease that causes widespread musculoskeletal pain. It primarily affects women and negatively impacts many aspects of a person’s psychological and social life. This study aimed to compare the effectiveness of cognitive therapy based on mindfulness and compassion therapy on automatic negative thoughts, psychological symptoms, pain intensity, and quality of life in patients with fibromyalgia syndrome. Methods & Materials This research is a quasi-experimental study with a pre-test-post-test design with two experimental and one control group. The statistical study population consisted of all individuals with fibromyalgia syndrome referred to Mehregan Pain Clinic in Mirdamad (District 3), Seyed Khandan Clinic (District 4), and Taleghani Hospital Pain Clinic (District 1) in Tehran City, Iran. Of them, 30 patients were randomly selected and divided into three groups of experimental 1, experimental 2, and control; each group will include 10 people. The instruments used in this study included the World Health Organization quality of life questionnaire (WHOQOL BREF), pain intensity questionnaire (PIS), psychological symptoms questionnaire (Anxiety, Stress and Depression [DASS]), and automatic negative thoughts (QNS). Ethical Considerations This study was approved by the Research Ethics Committee of Arak Branch, Islamic Azad University (Code: IR.IAU.ARAK.REC.1400.005). Results The analysis of covariance showed the effectiveness of both cognitive therapies based on mindfulness and compassion therapy on four variables of pain intensity, psychological symptoms, automatic negative thoughts, and quality of life (P<0.05). Comparing the two intervention methods showed that both therapies had almost the same effect on pain intensity, psychological symptoms, and automatic negative thoughts (P<0.05) but the effectiveness of mindfulness intervention on the quality of life was significantly higher than compassion intervention (P<0.05). Conclusion The results indicate that cognitive therapy based on mindfulness and compassion therapy are suitable for people with fibromyalgia under appropriate treatment. [ABSTRACT FROM AUTHOR]