Objectives: This study was conducted to determine the efficacy of mindfulness-based cognitive therapy (MBCT) on psychological symptoms and quality of life (QoL) in patients with systemic lupus erythematosus (SLE). Methods: We conducted a randomized single-blind clinical trial in patients with SLE referred from the Imam Ali Clinic in Shahrekord, southwest Iran. The patients (46 in total in two groups of 23 each) were randomly assigned into the experimental and control groups. Both groups underwent routine medical care, and the experimental group underwent eight group sessions of MBCT in addition to routine care. The patient,s QoL was assessed using the General Health Questionnaire-28 and 36-Item Short Form Health Survey before, after, and six months after intervention (follow-up). Results: A significant difference was seen in psychological symptoms and QoL between MBCT and control groups immediately after the intervention and at follow-up (p ≤ 0.050). However, the difference was not significant for the physical components of QoL (p ≥ 0.050). Conclusions: MBCT contributed to decreased psychological symptoms and improved QoL in patients with SLE with a stable effect on psychological symptoms and psychological components of QoL, but an unstable effect on physical components.