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Depression is one of the most prevalent mental disorders in the working population. About 10% of workers currently have at least one mental disorder; approximately 2%–7% of the workforce experiences depression. There is growing awareness of the social and economic costs of depression and its heavy workplace burden. Recognising the heterogeneity of workers’ experiences of depression, there have been suggestions to focus interventions on individual depression symptoms and symptom clusters (i.e., profiles) rather than depression severity alone. Our analyses explore the question, ‘What is the relationship between depression symptom profiles and work productivity loss?’These analyses use a population-based sample of 2219 employed adults living in Ontario, Canada. Based on PHQ-8 items, depression symptom profiles were identified using cluster analysis methods. Four work productivity loss dimensions (WPLD) were examined: (1) limitations handling time, (2) physical limitations, (3) mental-interpersonal limitations and (4) output demands limitations from the Work Limitations Questionnaire. Associations between the WPLD and the symptom profiles were examined using multiple linear regression.Depression symptom profile groups differed in the magnitude of productivity losses. The group experiencing the highest severity across all symptoms had 5%–20% more work productivity losses in all four WPLD compared to the other groups. The group with the most difficulty concentrating had 4%–13% greater productivity losses related to mental-interpersonal limitations than other groups. This group along with those who experienced disruption in sleep, energy, and appetite had 8%–12% greater productivity losses related to limitations handling time than other groups.Our results suggest workers have different experiences of depression. To assist workers with depression to continue being productive, attention should be paid to the combinations of types of difficulties and specific job characteristics. By understanding the specific challenges, work accommodations can be designed to target specific challenges workers face.