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OBJECTIVE: To evaluate the relationship between self-reported quality of life and disease activity, damage, impairment, disability, and handicap in systemic lupus erythematosus (SLE). METHODS: In this cross sectional study disease activity was measured with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and the Systemic Lupus Activity Measure (SLAM), and damage by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) damage index (SDI). Quality of life was assessed by the Medical Outcome Survey Short Form 36 (SF-36) and the EuroQol (EQ-5D). Multiple linear regression was used to identify significant associations of patients' health status, and logistic regression was used to evaluate the relationship of each of the 5 dimensions of the EQ-5D in terms of impairment, disability, and handicap. RESULTS: Damage was associated with the Physical Function (PF) and Social Function subscales of the SF-36. Disease activity was associated with the General Health (GH) subscale. Ability to carry out usual activities was strongly related to PF and GH as well as to global rating of the thermometer rating scale of the EQ-5D. Role Physical (RP) and Bodily Pain (BP) of the SF-36 were also associated with the EQ-5D rating scale. In addition, patients' ratings of anxiety and depression were strongly related to the Mental Health (MH) summary scale of the SF-36. CONCLUSION: Perceived health status of patients with lupus was associated with disease activity, damage, role physical, bodily pain, capacity for usual activity, and mobility. EQ-5D is a valid instrument for the measure of health related quality of life in SLE.