Problem Evidence is emerging of adverse associations between prolonged sitting at work and physical health, yet little is known about occupational sitting and mental health. This study examined associations between occupational sitting and psychological distress in employed adults, independent of leisure-time physical activity. Methods A survey of 3367 state government employees (mean age 46.2 years, 71.9% women) was conducted in Tasmania, Australia, during 2010 as part of an evaluation of workplace health and wellbeing programs. The Kessler Psychological Distress Scale (K10) was used to measure psychological distress, and participants reported time spent sitting at work on a typical day. Physical activity was assessed using the International Physical Activity Questionnaire (IPAQ). Ratios of prevalence (PR) for categories of psychological distress were estimated by log multinomial regression separately for men and women, and with adjustment for age, marital status, effort-reward imbalance and leisure-time physical activity. Results Average reported occupational sitting time was 4.8 (Standard Deviation SD=2.5) hours for men and 4.2 (SD=2.7) hours for women. Compared to those sitting at work less than 3 hours/day, men sitting more than 6 hours/day had increased prevalence of moderate psychological distress (adjusted PR=1.90, 95%CI 1.22, 2.95), and women sitting more than 6 hours/day had an increased prevalence of moderate (adjusted PR=1.25, 95%CI 1.05, 1.49) and high (adjusted PR=1.76, 95%CI 1.25, 2.47) distress. Conclusion The current study found an association between occupational sitting and intermediate levels of psychological distress, independent of leisure-time physical activity. Reducing occupational sitting time may have mental health benefits.