Objectives: To quantify differences in health-related quality of life, 5-year mortality risk, and direct and indirect costs between SLE patients early in the course of disease and controls, and to assess the association, among patients, between demographic and clinical characteristics and these outcomes. Methods: Multiple dimensions of the burden of disease were measured in an inception cohort of 265 SLE patients and 355 controls. The study includes two data collection periods: the baseline study (1997-1999) and follow-up study (2001). Results: Using a previously validated 8-item short form health-related quality of life instrument (SF-8), physical component scores were 7.7 points lower (p < 0.0001), and mental component scores were 1.8 points lower (p = 0.07) in cases compared with controls, adjusting for age, sex, race, state and education. Among cases, physical component scores of the 16-29 year olds and 30-49 year olds were 5.6 and 4.1 points higher, respectively, compared with the 50 and older group. Survival rates were significantly reduced in cases: by 60 months after diagnosis, 8.7% of cases compared with 0.28% of controls had died (p<.0001). Predictors of mortality in cases included age, gender, and ethnicity, with a hazards ratio of 1.04 (95% CI 1.01, 1.06) per one-year increment in age, 2.5 (95% CI 1.0, 5.9) for males compared with females, and 2.0 (95% CI 0.89, 4.6) for African-Americans and other minorities compared with whites. Annual mean direct costs for health care was $12,375 (sd 13723) in cases compared with $3,718 (sd 6135) in controls (p <.0001); differences were also seen in the median costs ($8,008 compared with $2,207 in cases and controls, respectively). Predictors of higher costs among cases were low education level (less than high school), renal disease and serositis. Forty-seven cases (24%) compared with 8 (3%) controls reported they had stopped working because of their health, resulting in an average indirect cost of lost wages of $5113 compared to $750 in cases and controls, respectively. Conclusions: Significant differences in quality of life scores, mortality risk, direct and indirect costs demonstrate the multidimensional burden of SLE.