Background: This study aimed to explore perceived work stress and its association with burnout, compassion fatigue, and compassion satisfaction and the mediating effect of psychological flexibility on these relationships. Method: Two hundred and fifty-one disability support workers across Australia reported on work stress, psychological flexibility, burnout, compassion fatigue, and compassion satisfaction through an online anonymous survey. Results: Perceived work stress was found to have a significant relationship with burnout, compassion fatigue, and compassion satisfaction. Psychological flexibility had a significant mediating effect on all three relationships. Conclusion: These results highlight the role that psychological flexibility has in response to work stress and the development of burnout, compassion fatigue, and compassion satisfaction in disability support workers.