PURPOSE: This prospective study used the framework of ICF components to investigate the magnitude and direction of association between body functions (depression/anxiety symptoms), activity (limitations in work activities), participation (sickness absence), and environment (psychosocial aspects) in the workplace setting. METHODS: A cohort of employees completed a self-report survey at baseline and 6 months follow-up, with analysis restricted to those with at least one health condition (n = 204). Self-report measures of depression/anxiety symptoms, limitations in work activities, sickness absences, and psychosocial work environment were mapped to the corresponding ICF component. The prospective association between these components was modelled using relative risks (RR) estimated from log-binomial regression. RESULTS: Depression/anxiety symptoms were more likely to be an outcome of other ICF components, rather than a risk factor. Sickness absence, limitations in work activities, and work environment all conferred a greater than two-fold risk of depression/anxiety symptoms 6 months later. CONCLUSIONS: The ICF offers a valuable approach to understanding the contextual influences on employee mental health and work disability. Further application of the ICF framework to mental health should improve the environmental components and encourage a wider adoption of the ICF by mental health researchers and practitioners.