Work stressors are increasingly recognized as potentially important determinants of mental health status. We examined such relationships using a structural equation modelling approach with data on adult, working Canadians who participated in the first wave of the National Population Health Survey (NPHS). Work stressors formed a composite construct with paths from psychological demands, decision latitude, work social support and job insecurity, each measured through a reduced version of the Job Content Questionnaire. Life stressors also formed a composite construct composed of chronic stressors and recent life events. Psychological distress was the outcome, mediated by the latent effect constructs of mastery and self-esteem. Work stressors had consistently positive total effects on distress (sum of standardized path coefficients from 0.004 to 0.153 across gender-occupation strata), with all of these effects mediated through reduced self-esteem and mastery (work stressors to these mediators: -0.188 to -0.413). Life stressors had larger positive total effects on distress (0.462 to 0.536), with the majority of these effects direct.