Objectives : This study examined whether serious psychological distress (SPD) is associated with occupational injury among US employees. Methods : The employed population aged 18-64 years was examined (n=101,855) using data from the National Health Interview Survey (NHIS) 2000-2003. SPD was measured using the Kessler 6-item Psychological Distress Scale (K-6), a screening scale designed to identify persons with serious mental illness. The predicted marginal prevalence of psychological distress and occupational injury with the adjusted odds ratio were estimated using multiple logistic regression analyses. Results : The age-adjusted 3-month prevalence of occupational injury was $0.80{pm}0.12%$ in workers with SPD, which was 37% greater than in workers without SPD ($0.58{pm}0.03%$). The odds of occupational injury in workers with SPD were higher compared to workers without SPD (OR=1.34, 95% CI=0.93-1.92), after controlling for sex, age, race, education, occupation, and activity limitation by at least one medical condition. Male, service and blue collar occupation, and activity limiation by co-morbidity showed significantly higher odds of occupational injury for workers with SPD. Conclusions : The findings suggest that SPD accounts for an increased likelihood of occupational injury among US employees. A further longitudinal study is needed to differentiate the mechanism or causal pathways linking individual injury risk at the workplace, SPD, and socioeconomic factors.