The objectives of this study were to investigate whether psychological job demands, personal control and social support affect the negative health measure of depression differently than the positive measure of work engagement and to investigate whether work engagement mediates the effects of job demands and resources on the level of depression. We discuss the implications of using engagement as an outcome measure in workplace health promotion. We performed a cross-sectional questionnaire study among a general working population in Norway (n = 605). In the multivariate analysis, high psychological job demands as well as high control and social support correlated significantly with high work engagement. High demands as well as low control and social support correlated significantly with high levels of depression. When we included engagement as an independent variable together with demands, control and social support in the multivariate analysis, the positive correlation between demands and depression remained as well as the significant correlations between the level of depression and control and social support became non-significant. This indicates that engagement mediates the effects of control and social support on the level of depression. Encouraging enterprises to improve engagement in addition to focusing on preventing diseases may be worthwhile in workplace health promotion. Promoting engagement may have more positive organizational effects than a more traditional disease prevention focus, because engagement is contagious and closely related to good work performance and motivation.