BACKGROUND: Systemic lupus erythematosus (SLE) is characterized by a range of symptoms that often cluster together, impacting the quality of life (QoL) of affected individuals. OBJECTIVE: To delineate the composition of symptom clusters in patients with SLE and analyze their correlation with QoL, thus providing a basis for symptom management. METHODS: Using convenience sampling, 201 patients were recruited. Data were collected using a general information questionnaire, SLE Symptom Checklist and Lupus Quality of Life scale. Symptom clusters were identified using exploratory factor analysis, and their correlations with QoL were analyzed using Spearman correlation analysis. RESULTS: The most common symptom among patients was fatigue (64.7%). Five symptom clusters were identified: fatigue-related symptoms, weight gain-related symptoms, itch-pain-related symptoms, skin change symptoms, and body image symptoms. Fatigue-related, weight gain-related, and body image symptom clusters showed significant negative correlations with overall QoL scores and scores in various dimensions ( CONCLUSION: Patients with SLE exhibit significant symptom clusters correlating with overall QoL. Such data highlight the need for nurses to evaluate symptom clusters and intervene in related factors, enhancing QoL.