Objective: To examine the risk factors for self-reported work disability in patients from the LUpus in Minorities: NAture vs. Nurture cohort with systemic lupus erythematosus (SLE). Methods: Patients with SLE of Hispanic (Texas and Puerto Rico), African American and Caucasian ethnicity were studied. Work disability was defined by patients' self-report. Only patients known to be employed at the baseline visit were included. The probabilities of self-reporting work disability over time were examined by the Kaplan-Meier method; differences between ethnic groups were examined by the log-rank test. The relationship of baseline socioeconomic-demographic, clinical, behavioural and psychological features with work disability was examined by standard statistical tests. Variables with p ≤ 0.10 in these analyses were examined by logistic regression. Results: The rate of self-reported work disability among the 273 patients studied was 19% at 5 years; it was numerically higher for the African Americans (25%) than for the Hispanics from Texas (19%) and the Caucasians (18%). The rate for the Hispanics from Puerto Rico was 7% at 2 years; 5-year rates could not be estimated for this ethnic subgroup (shorter follow-up in the cohort). In the regression analysis, age, male sex, poverty, total disease duration, disease activity and damage accrual were predictors of work disability. Conclusions: The rate of work disability was 19% at 5 years. Patients with SLE with more severe disease and with lower socioeconomic status are at high risk of becoming disabled. The toll SLE imposes could possibly be reduced in patients at risk if, in addition to medical treatment, services needed to overcome their disadvantageous socioeconomic status are provided.