Differences in fatigue and psychological distress across occupations were examined among 8521 employees participating in the Maastricht Cohort Study of “Fatigue at Work.” Additional information on the perceived psychosocial work environment was incorporated. A total of 131 occupations, classified according to the Netherlands Standard Classification of Occupations 1992, were studied. Results showed that occupation as a proxy index of the “objective” work environment adds little explanatory information beyond perceived measures of the work environment. Although “occupation” seems to be an easy entree for intervention, focusing on occupation exclusively to prevent, or at least reduce, fatigue and psychological distress may be inadequate. Supplementary information about the perceived work environment of the job occupant is needed to develop preventive measures on the individual level. Further research, including a longitudinal analysis, is required to elucidate the complex relation between occupation, psychosocial risk factors, and fatigue and psychological distress.