OBJECTIVE: Health related quality of life (HRQOL) over course of the disease was ascertained in SLE patients from LUMINA, a multiethnic US cohort, using the SF-36-derived utility measure, the SF-6D. METHODS: All available visits were examined to predict HRQOL using either variables from the baseline or enrollment visits or from the preceding visits. The physical and mental component summary (PCS and MCS, respectively) measures of the SF-36 were also examined. A total of 2662 visits from 588 SLE patients were included; 90% of the patients were women, 19% Hispanic-Texans, 17% Hispanic-Puerto Ricans, 35% African Americans and 29% Caucasians. The patients' mean (SD) SF-6D was 0.6 (0.1). RESULTS: In multivariable analyses, Hispanic-Texan ethnicity and higher levels of social support were predictors of HRQOL whereas older age, poverty, greater disease activity and damage and higher levels of fatigue, helplessness and abnormal illness-related behaviors were negative predictors. Prior SF-6D was the strongest variable predictive of subsequent HRQOL, when included. The analyses in which the PCS and MCS were examined as end-points were, overall, consistent with the SF-6D results. CONCLUSION: We conclude that the SF-6D index provides an adequate measure of self-perceived HRQOL and that patients' self-perception of HRQOL is influenced by disease and non-disease related factors.