Introduction: Psychosocial work environment has been related to many negative health outcomes in different workforces. However, evidence in this regard is still limited in the case of transport workers, and most of the tools used in research, often excessively generic, do not fully consider the specific key stressors, and adverse issues present in the psychosocial environment of professional driving. Objective: Thus, the purpose of this study was to obtain a complete description of the validation of measurement applied to psychosocial factors at work in professional drivers, using the Enterprise version (2018) of COPSOQ-III. Methods: The data was collected from 726 Spanish professional drivers, and the analyses were conducted using the competitive Confirmatory Factor Analysis or CFA, obtaining basic psychometric properties and an optimized structure for the instrument applied to active transport workers. Results: The results suggest a clear factorial structure, high factorial weights, internal consistency, and an improved adjustment to the psychosocial conditions of this group, excluding a set of items with low psychometrical adjustment and keeping the five-factor structure of the questionnaire: demands, influence and development, interpersonal relationships and leadership, job insecurity, and strain-effects and outcomes. Conclusion: Overall, what was found in this study supports the hypothesis that the validated version of COPSOQ in professional drivers, together with complementary information sources specific for their work environment, may have a relevant research value and some important practical implications for the improvement of the occupational safety, and health within the typically vulnerable industry of transportation.