This 386-participant study investigated the structural and psychometric properties of the Spanish version of the Occupational Depression Inventory (ODI). Exploratory structural equation modeling bifactor analysis revealed that the ODI meets the requirements for essential unidimensionality. Measurement invariance held across our sample and the English- and French-speaking samples used in the ODI’s initial validation study. Mokken scale analysis indicated that (a) the scalability of the instrument was strong, (b) no violations of monotonicity or local independence were present, and (c) invariant item ordering was sufficiently accurate. The ODI’s reliability was optimal. The ODI exhibited both convergent validity and discriminant validity vis-à-vis a job-unrelated measure of depression. Furthermore, occupational depression correlated substantially, and in the expected direction, with objective cognitive performance and 10 widely studied worklife characteristics. This study suggests that the ODI’s Spanish version has excellent structural and psychometric properties and can be confidently employed by occupational health specialists.