BACKGROUND The studies of association of disease activity and damage with health-related quality of life (HRQOL) in lupus have shown equivocal results and has not been studied in Thailand. OBJECTIVE To examine the HRQOL and to examine the association between HRQOL and SLE disease severity (disease activity and damage) in Thai SLE patients. MATERIAL AND METHOD The Short Form-36 (SF-36) was applied in 95 consecutive SLE patients. At the time of HRQOL assessment, all patients were evaluated for disease severity [disease activity as measured by Mexican Systemic Lupus Erythematosus Disease Activity Index (Mex-SLEDAI) and damage as measured by the Systemic Lupus International Collaborating Clinic/American College of Rheumatology (SLICC/ACR) damage index (SDI)]. The association between physical (PCS) and mental component summary (MCS) of the SF-36 and disease severity were examined by Pearson's correlation. RESULTS Ninety-five SLE patients (93 females and 2 males) were included (mean age 39.84 +/- 10.91). The mean disease duration was 115 +/- 83 months. The mean scores of MCS and PCS were 45.5 +/- 9.5 and 41.1 +/- 9.3, respectively. The higher SDI scores were correlated with lower PCS but not the MCS (PCS, r = -0.411, p < 0.001). There was no correlation between HRQOL (both MCS and PCS) and disease activity. CONCLUSION PCS of the SF-36 was inversely correlated with damage index in Thai SLE patients.