Objective. To determine the prevalence, accrual over time, and risk factors of work disability in patients with systemic lupus erythematosus (SLE). Methods. We studied 432 patients from an inception cohort. Work disability was measured from a single self-report question. Results. Of 432 patients, 88% were women and 73% were white. Within the first year of diagnosis, 47% of patients were employed, 7% had a disability, and 7% were on sick leave. Overall, work disability was found in 98 (23%) patients. Risk factors for work disability found in the multivariate regression analysis were younger age at diagnosis, less education, fibromyalgia, hypertension, higher first-visit SLEDAI-2K score, and lower first-visit SF-36 score. Conclusion. Work disability is frequent in patients with SLE, with a cumulative prevalence of 23%. Work disability was associated with a complex array of health factors, including comorbidity, physical and mental health limitations, and clinical features of lupus, that warrant increased attention in future research.