Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease that can cause significant kidney disease. Our goal was to assess the relative mortality risk associated with SLE in pediatric and adult populations with end-stage renal disease (ESRD) maintained on hemodialysis (HD). We performed Kaplan-Meier survival analysis from data collected by the United States Renal Data System (USRDS) in strata of pediatric and adult patients. This file includes data on all Medicare-reimbursed renal replacement patients. Cox proportional hazard models were used to assess mortality after adjusting for race and gender. Subjects were censored at transplantation or at end of follow-up. Pediatric patients with ESRD secondary to SLE had a 2-fold increased risk of death compared with other pediatric patients with ESRD (hazard ratio [HR]: 2.4, 95% confidence interval [CI]: 1.5-3.7). Adult patients with ESRD secondary to SLE were also at increased risk of death compared with other adult patients (HR: 1.7, 95% CI: 1.2-2.7). The most common causes of death in both pediatric and adult patients with SLE were cardiovascular disease and cardiac arrest. Our study demonstrates that there is a significant increase in mortality secondary to cardiovascular disease in pediatric and adult patients with ESRD secondary to SLE. Patients with ESRD secondary to SLE may need aggressive monitoring for traditional risk factors for atherosclerosis and the diagnosis of SLE alone may be an independent risk factor for death in patients with ESRD.