The objective of this study was to determine risk factors predicting seizures and damage caused by seizures in a multi-ethnic systemic lupus erythematosus cohort (PROFILE) that includes systemic lupus erythematosus patients (n = 1295) from five different US institutions. Only patients with seizures after systemic lupus erythematosus diagnosis (incident) were included in the analyses of clinical seizures (80/1295, 6.2%), but all patients (prevalent and incident) were included in the analyses of damage caused by seizures (51/1295, 3.9%). We examined socioeconomic-demographic, clinical, and genetic variables predictive of clinical seizures and damage from seizures by Cox proportional hazard ratios (HR) and 95% confidence intervals (CI). Independent predictors of a shorter time to the occurrence of clinical seizures were younger age (HR = 1.0; 95% CI 0.9-1.0), having Hispanic-Texan ethnicity (HR = 2.7; 95% CI 1.3-5.7) or African-American ethnicity (HR = 1.8; 95% CI 1.0-3.1), and the previous occurrence of a cerebrovascular accident (HR = 3.3; 95% CI 1.6-7.1) or an episode of psychosis (HR = 2.4; 95% CI 1.1-5.0), whereas the previous occurrence of photosensitivity (HR = 0.5; 95% CI 0.3-0.9) was the only independent predictor of a longer time to the occurrence of clinical seizures. Independent predictors of a shorter time to the occurrence of damage caused by seizures were younger age (HR = 1.0; 95% CI 0.9-1.0), male gender (HR = 2.4; 95% CI 1.1-5.4), and the occurrence of a previous cerebrovascular accident (HR = 2.7; 95% CI 1.0-7.0) or an episode of psychosis (HR = 4.7; 95% CI 2.3-9.9). No allele from the candidate genes examined (HLA-DRB1, HLA-DQB1, FCGR2A, FCGR3A, or FCG3B) predicted clinical seizures or damage caused by seizures.