Well-being at work has been shown to be influenced by job characteristics and individual differences in coping styles. This study investigated the relationships between job demands, control, social support, efforts, rewards, coping, and attributional style in predicting anxiety, depression, and job satisfaction in a sample of 307 university employees from the UK. Results were compared to those from a sample of 120 members of the general population. Workplace demands, intrinsic and extrinsic effort, and negative coping and attributional behaviors were associated with high levels of depression and anxiety and low job satisfaction in university employees. Rewards, social support, job control, and positive coping and attributional behaviors were associated with lower levels of depression and anxiety and high job satisfaction. The study adds to the growing research on university samples by showing that a transactional approach should be adopted. This has implications for interventions and suggests that rather than just trying to change job characteristics one should identify at-risk individuals in this population and help them adopt appropriate positive coping styles.