The aim of the present study was to explore: the main effect of empowerment on burnout; empowerment as a mediator between the work environment and burnout; and empowerment as a moderator of the association between the work environment and burnout. In order to explore these effects, multiple regression analyses were performed on questionnaire data from 838 registered nurses and 518 assistant nurses in Sweden. The analyses showed that: empowerment has a negative association to burnout; empowerment has a mediating effect between the work environment (especially for control and social support) and burnout; and the moderating effect of empowerment on the association between the work environment and burnout was weak. The results suggest that: empowerment explains variation with regard to burnout over and above what can be explained by established work situation dimensions; the improvement of the work environment is associated with a higher sense of empowerment which, in turn, is related to lower degrees of burnout; and individual and group differences should be considered in workplace health promotion.