The aim of this study was to estimate the nationwide prevalence and incidence of systemic lupus erythematosus (SLE) in South Korea. National Health Insurance claims data covering almost all Koreans (~50 million) during 2006-2010 were analyzed. Individuals with SLE were identified if (1) they had experienced at least one hospitalization for SLE (International Classification of Diseases, 10th revision code M32), (2) they had taken at least one concomitant prescription of immunosuppressant and hydroxychloroquine, or (3) they had taken anti-dsDNA antibody (≥2) or complement tests (≥2) during each calendar year. Incident cases were defined only if they had not been SLE prevalent for the preceding 2 years and had been SLE prevalent for 2 years consecutively thereafter. The annual prevalence (per 100,000) increased slightly from 20.6 [95% confidence interval (95% CI) 20.2-21.0] in 2006 to 26.5 (95% CI 26.0-27.0) in 2010, and the incidence (per 100,000) ranged between 2.5 (95% CI 2.4-2.6) in 2008 and 2.8 (95% CI 2.7-2.9) in 2009. The number of SLE-prevalent female patients outnumbered SLE-prevalent male patients by approximately sixfold, with a female-to-male incidence ratio of ~9:1. The prevalence and incidence of SLE increased significantly with age, regardless of sex, to a peak the age of 30-39 years. However, while both of them significantly decreased thereafter in females, this tendency was not observed in males.