Objective: Unemployment is common among individuals with Multiple Sclerosis (MS) and is associated with significant socioeconomic burden. Several MS-related factors have been found to associate with employment status including fatigue, depression, cognitive problems, and motor difficulties. However, few studies have examined these factors collectively in predicting employment. Method: Fifty-seven individuals with MS participating in a research study of cognitive, emotional, and social factors related to MS were examined. Composite scores were created using factor analysis that represented cognition, fatigue, depression, and motor function. These composite scores, along with disease duration and age, were explored as predictors of employment status (working, not working) via logistic regression. Models of mediation were also investigated. Results: A model including composites of motor function, cognition, depression, and fatigue significantly predicted employment status, χ2(4) = 10.16, p=. 038, Nagelkerke R2 = .22. However, only the cognitive composite was found to be a significant predictor after controlling for all other variables in the model. Results of a mediation analysis using 1, 000 bootstrap samples indicated that the cognitive composite significantly mediated both the effect of age (indirect effect=. 027, 95% CI [.0005, 1160]) and disease duration (indirect effect=. 042, 95% CI [.0067, .1059]) on work status. Conclusion(s): Cognitive function predicts employment status above and beyond fatigue, depression, and motor function. Additionally, cognitive function partially mediates the effect of age and disease duration on employment status. Interventions targeting cognitive difficulties in MS may be effective in allowing individuals to maintain employment.