Employers who are developing strategies to reduce health-related productivity loss may benefit from aiming their interventions at the employees who need them most. We determined whether depression’s negative productivity impact varied with the type of work employees performed. Subjects (246 with depression and 143 controls) answered the Work Limitations Questionnaire and additional work questions. Occupational requirements were measured objectively. In multiple regression analyses, productivity was most influenced by depression severity (P < 0.01 in 5/5 models). However, certain occupations also significantly increased employee vulnerability to productivity loss. Losses increased when employees had occupations requiring proficiency in decision-making and communication and/or frequent customer contact (P < 0.05 in 3/5 models). The Work Limitations Questionnaire can help employers to reduce productivity loss by identifying health and productivity improvement priorities.