Objective. To determine the baseline factors predictive of self-reported health-related quality of life (HRQOL) early in the course of systemic lupus erythematosus patients (SLE) from a multiethnic LUMINA (Lupus in Minorities: Nature versus nurture) cohort. Methods. LUMINA patients with ≥2 visits were studied. Self-reported HRQOL was examined with the 8 subscales and 2 summary measures (the Physical Component Summary [PCS], and the Mental Component Summary [MCS]) of the Short Form 36 (SF-36). Bivariable and multivariable analyses were done with the PCS, MCS and 8 subscales as the dependent variables. The analyses were performed including and excluding the corresponding SF-36 measure from the independent variables. Age, sex, and ethnicity were included in all models. Time was modeled in all regressions. Results. A total of 1,351 visits (346 patients [80 Hispanics-Texas, 34 Hispanics-Puerto Rico, 126 African Americans, and 106 Caucasians]) were included in these analyses. Mean ± SD PCS and MCS scores were 36.7 ± 12.0 and 46.6 ± 11.5 respectively. The scores for the eight subscales of the SF-36 were also lower than those for the general population. Baseline SF-36 measures were highly predictive of subsequent HRQOL. In the same set of regressions, older age was found to consistently predict poor self-reported HRQOL whereas fibromyalgia, helplessness, fatigue, and abnormal illness-related behaviors were also predictive, but less consistently. Estimated adjusted variances in these regressions ranged from 23% (Role-Emotional [RED]) to 43% (Physical Functioning [PF]). Conclusion. In patients with SLE, poor baseline HRQOL was highly predictive of subsequent poor HRQOL. Other predictive variables of poor functioning were primarily psychological/behavioral and socioeconomic-demographic.