Objective. To determine the features associated with mortality in a multiethnic US cohort of patients with systemic lupus erythematosus (SLE) within 5 years of study onset. Methods. Socioeconomic and demographic features (age, gender, ethnicity, marital status, education, occupation, poverty, and health-related behaviors [drinking, smoking, exercising]), clinical and immunologic features (disease duration, disease onset type, disease activity according to the Systemic Lupus Activity Measure [SLAM], disease damage according to the Systemic Lupus International Collaborating Clinics [SLICC] Damage Index [SDI], number of American College of Rheumatology criteria at diagnosis, organ system manifestations, fatigue and pain ratings, and medication usage and autoantibodies), immunogenetic features (HLA class II genotypes), and behavioral and psychosocial features (social support, illness-related behaviors, and helplessness), as obtained at enrollment into the study, were compared between survivors and deceased patients. Logistic regression analysis was used to determine significant independent risk factors for mortality. Results. Within 5 years of study onset, 34 of 288 patients have died. Fourteen deaths could be directly attributed to SLE and 11 to infections. In 1 patient the cause of death could not be determined. In the remaining 8 patients the cause of death was neither infectious nor disease-related. There were 10 deaths among Hispanics, 18 among African Americans, and 6 among Caucasians (P<0.05). Variables associated with mortality in the univariable analyses included poverty, less than full-time employment, difficulty in accessing health care, shorter disease duration, cardiovascular and renal involvement, higher serum creatinine levels and lower hematocrit values, higher SLAM and SDI scores, lower use of antimalarial drugs, and higher use of (some) immunosuppressants. Specific autoantibodies and class II HLA genotypes were not associated with mortality. Poverty and higher baseline SLAM and SDI scores were independently associated with mortality in the multivariable analyses. Conclusions. Disease activity, disease damage, and poverty appear to be the most important determinants of mortality in this multiethnic US cohort of SLE patients. These results have applicability to the management of patients with SLE, a disease that more severely affects disadvantaged minority population groups.