BACKGROUND: Most studies on the psychosocial working environment have focused on evaluating the isolated effect of individual psychosocial work factors or looked at effects through a lens of theories such as job strain or effort-reward imbalance. However, to fathom the intricate nature of workers' experience of occupational strain, there is a need to investigate the combined and cumulative effects of multiple exposures to psychosocial work factors on workers' health. METHODS: In this prospective cohort study, we created an additive index (range 0-4) on number of baseline exposures to quantitative demands, emotional demands, role conflicts, and workplace bullying. Via logistic regression and Cox regression, we estimated the association between the additive index of psychosocial work factors and depressive disorder and long-term sickness absence (LTSA). We assessed the onset of depressive disorder using the Major Depression Inventory at 6-month follow-up and the onset of LTSA using a national register during 12-month follow-up. RESULTS: For onset of depressive disorder, high exposure to any one [odds ratio (OR) 2.98], two (OR 3.14), three (OR 6.44) and all four (OR 9.62) adverse psychosocial work factors predicted a statistically significant increased risk. For onset of LTSA, high exposure to any one [hazard ratio (HR) 1.13], two (HR 1.67), three (HR 2.31) and all four (HR 4.04) psychosocial work factors predicted an increased risk. The two latter associations were statistically significant. Trend tests indicated an exposure-response relationship for both outcomes. CONCLUSIONS: Workers reporting exposure to multiple adverse psychosocial work factors had a higher risk of developing depressive disorder and LTSA.