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Background: The psychological effects of systemic lupus erythematosus (SLE) are tremendous. This pilot mixed-methods randomized controlled trial aimed to evaluate the effects of a mindfulness-based stress reduction (MBSR) adapted protocol on psychological distress among SLE patients., Methods: 26 SLE patients were randomly assigned to MBSR group therapy ( n = 15) or a waitlist (WL) group ( n = 11). An adapted MBSR protocol for SLE was employed. Three measurements were conducted: pre-intervention, post-intervention and 6-months follow up. A sub-sample ( n = 12) also underwent qualitative interviews to assess their subjective experience of MBSR., Results: Compared to the WL, the MBSR group showed greater improvements in quality of life, psychological inflexibility in pain and SLE-related shame. Analysis among MBSR participants showed additional improvements in SLE symptoms and illness perception. Improvements in psychological inflexibility in pain and SLE-related shame remained stable over six months, and depression levels declined steadily from pre-treatment to follow-up. Qualitative analysis showed improvements in mindfulness components (e.g., less impulsivity, higher acceptance), as well as reduced stress following MBSR., Conclusions: These results reveal the significant therapeutic potential of MBSR for SLE patients. With its emphasis on acceptance of negative physical and emotional states, mindfulness practice is a promising treatment option for SLE, which needs to be further applied and studied.