Social workers are expected to remain engaged and empathic with clients in complex situations that often involve intense pain, trauma, and conflict. Although empathy is commonly assumed to be a critical factor in effective helping, empathy without sufficient emotional separation may place helpers at higher risk of secondary-stress reactions. Mo studies have examined mindfulness in relation to compassion fatigue or compassion satisfaction, nor in relation to burnout specifically among social workers. In addition, further study is needed to examine the effect of practitioner empathy and emotional separation on compassion fatigue, burnout, and compassion satisfaction. This study was an attempt to fill this gap. This correlational study used cross-sectional data to explore the constructs of mindfulness, empathy, emotional separation, compassion fatigue, compassion satisfaction, and burnout in a random sample of licensed clinical social workers in a Southern state of the USA. Findings show mindfulness and emotional separation are significantly associated with compassion satisfaction and burnout, and emotional separation is significantly associated with compassion fatigue. These results suggest that increased emphasis on the intentional management of internal emotional states may be as important for clinicians as it is for clients, and that professional training programs should consider how best to teach such skills.