In this study, we investigated the role of psychological empowerment as a protective factor for burnout among workers exposed to work-related stressors (e.g. daily hassles, overload, job changes). A cross-sectional questionnaire study was conducted, with a convenience sample of 401 healthcare workers. Hierarchical multiple regressions were performed to test main and moderating effects of empowerment cognitions. Results revealed partial support for the hypotheses. Only the job meaningfulness cognition exerts a beneficent main effect on all burnout symptoms beyond the effect of stressors. Some moderating effects differing according to burnout dimensions were also found. Most interestingly, high levels of empowerment cognitions accentuate the effect of change-related resources in the reduction of emotional exhaustion. Because psychological empowerment has beneficial effects, organizations could rely on different strategies to enhance it.