Patients with systemic lupus erythematosus experience a decreased health-related quality of life due to disease activity, multisystem organ involvement and frequent hospitalization. High levels of anti-double-stranded DNA antibodies are associated with renal disease, a primary cause of morbidity and mortality in systemic lupus erythematosus, and progressive cognitive dysfunction. Post hoc analyses of two clinical trials of abetimus sodium identified responders with sustained reductions in anti-double-stranded DNA antibodies. At 6 and 12 months, responders reported improvement in health-related quality of life, as measured by the Medical Outcomes Survey Short Form 36, compared with no change or deterioration in nonresponders. Sustained reductions in anti-double-stranded DNA antibodies, regardless of treatment group, led to clinically meaningful improvements in patient-reported health-related quality of life.