To determine the relationship between cognitive impairment and employment in patients with systemic lupus erythematosus (SLE). A total of 167 consecutive patients with SLE were prospectively evaluated, and underwent standardized neuropsychological tests. Multivariate logistic regression was used to determine the likelihood of being unemployed, adjusting for sociodemographic characteristics, employment status at study entry, disease activity, disease duration, damage scores, and depression. At study entry, 118 (70.7%) of 167 patients were employed. In the multivariate analysis, after adjusting for confounders, unemployment was predicted by the number of cognitive domains impaired (odds ratio [OR] 1.76, 95% confidence interval [95% CI] 1.58-6.72), depression (OR 1.3, 95% CI 1.1-3.1), fewer years of education (OR 0.12, 95% CI 0.02-0.34), and the presence of anticardiolipin antibodies (OR 1.43, 95% CI 1.2-6.1). Complex attention (OR 1.7, 95% CI 1.2-3.6), memory (OR 3.1, 95% CI 1.5-6.2), and executive functions (OR 2.4, 95% CI 1.9-6.1) were predictors of unemployment at study entry. After 3 years, 61 (51.7%) of 118 patients were employed (OR 2.25, 95% CI 1.38-3.68; P = 0.001). The likelihood of being unemployed after 3 years was predicted by the number of cognitive domains impaired (OR 3.8, 95% CI 2.5-7.71), depression (OR 2.31, 95% CI 1.01-5.21), fewer years of education (OR 0.09, 95% CI 0.01-0.42), and the presence of anticardiolipin antibodies (OR 2.1, 95% CI 1.2-4.9). Complex attention (OR 2.2, 95% CI 1.1-3.8), memory (OR 3.6, 95% CI 2.1-6.4), executive functions (OR 1.8, 95% CI 1.2-7.3), and reasoning/problem solving (OR 1.9, 95% CI 1.4-7.2) were associated with unemployment after 3 years. The number of cognitive spheres, and especially attention, memory, and executive functions, are important factors associated with unemployment in patients with SLE.61680-7