<p>As business environments become increasingly competitive, interest in employees’ work engagement has grown. This study tested the hypothesis that the association between brain gray matter volume (GMV) and work engagement differs by occupation. Specifically, we compared knowledge workers with non-knowledge workers. Results indicated that the association between work engagement and GMV was positive among knowledge workers but negative among non-knowledge workers after adjusting for demographic and health-related variables. The observed effect sizes were modest, and the cross-sectional design does not permit causal inference. Nevertheless, the findings suggest that the neurobiological correlates of work engagement may differ across occupational contexts. One possible interpretation is that engagement among knowledge workers may be more closely aligned with autonomous and flexible forms of involvement, whereas engagement among other workers may be more likely to coexist with strain-related processes. To our knowledge, this is the first study to report an occupation-dependent association between brain structure and work engagement.</p>