BACKGROUND: Denmark, like other Western countries, is recently burdened by increasingly high social spending on employment consequences caused by ill mental health. This might be the result of high work demands affecting persons with ill mental health. Therefore, this study assesses to what extent depressive symptoms and high work demands, individually and combined, have an effect on employment consequences. METHODS: We conducted a population-based 7-year longitudinal follow-up study with baseline information from the year 2000 on socio-demographics, lifestyle, depressive symptoms and work demands. In total, 5785 employed persons, aged 40 and 50 years, were included. Information about employment status, sick leave and work disability was obtained from registers. Logistic regression models were used to measure separate and combined effects of depressive symptoms and work demands on job change, unemployment and sick leave during 2001-02 and work disability during 2003-07. RESULTS: After adjustment for covariates, high physical work demands and depressive symptoms had a graded effect on subsequent unemployment, sick leave and permanent work disability. Persons with both depressive symptoms and high physical demands had the highest risks, especially for sick leave, but the combined effect did not exceed the product of single effects. Persons who perceived high amount of work changed job significantly more frequently. CONCLUSION: Persons with depressive symptoms might have an increased risk of negative employment consequences irrespective of the kind and amount of work demands. This might be an effect on the level of work ability in general as well as partly the result of health selection and co-morbidity.