In this study, we aimed at testing the main hypotheses of the Job Demands-Resources model (JD-R) in a sample of employees (n = 205, mainly healthcare workers) of a long-term care institution located in Northern Italy. Hierarchical linear regression analyses show that almost all job demands considered were significantly associated with higher general psycho-physical exhaustion (beta ranging from 0.14 to 0.29), whereas more unfavourable scores in all job resources were associated with lower work engagement (from -0.27 to -0.51). However, also significant cross-over associations were observed, mainly between job resources and exhaustion, with effect sizes comparable with those found for the relationships between job demands and exhaustion. Hence, our study only partially supports the JD-R model. Implications of results for work-related stress management are finally discussed.