C-reactive protein (CRP), a biomarker of inflammation, has been associated with increased disease activity in rheumatoid arthritis. However, the association in systemic lupus erythematosus (SLE) remains unclear. We examined the association of CRP with self-reported disease activity in the Carolina Lupus Study and described differences by sociodemographic characteristics. The study included baseline and three-year follow-up data on 107 African-American and 69 Caucasian SLE patients enrolled at a median 13 months since diagnosis. Models estimated prevalence differences in the association of baseline CRP with self-reported flares, adjusting for age, sex, race and education. Active disease or flare was reported by 59% at baseline and 58% at follow-up. Higher CRP (>10 μg/ml vs. <3 μg/ml) was associated with a 17% (95% CI: −20, 53%) higher prevalence of flare at baseline and a 26% (95% CI: −9, 62%) higher prevalence of flare at follow-up. These CRP-flare associations were notably stronger in patients with lower education at baseline and in African Americans at follow-up. These findings suggest CRP may be a useful marker in studies of SLE health disparities