This study aimed to validate the recently developed Occupational Depression Inventory (ODI) in South Africa. A total of 327 employees (60% female) participated in the study. Bifactor exploratory structural equation modeling analysis indicated that the ODI can be considered essentially unidimensional. The ODI displayed strong scalability (e.g., scale-level H = 0.657). No monotonicity violation was detected. The reliability of the instrument, as indexed by Cronbach's alpha, McDonald's omega-total, Guttman's λ2, and the Molenaar-Sijtsma statistic, was highly satisfactory. Measurement invariance was observed across age groups, sexes, and ethnicities, as well as between our sample and the ODI's original validation sample. As expected, the ODI showed both a degree of convergent validity and a degree of discriminant validity vis-à-vis a measure of "cause-neutral" depressive symptoms. Moreover, the ODI manifested substantial associations, in the anticipated directions, with measures of work engagement, job satisfaction, and life satisfaction. Overall, the ODI exhibited excellent structural and psychometric properties within the South African context. Consistent with previous research, this study suggests that occupational health specialists can confidently rely on the ODI to investigate job-related distress.