Background: Expatriation and relocation into a new cultural context constitute a psychological journey marked by exposure to potentially traumatic events, the abandonment of the homeland and the effort of seeking safety and a new beginning at all levels. Objective: The aim of this study was to investigate the Professional Quality of Life in Greek health professionals working with refugees and migrants. Methods: The Professional Quality of Life Scale (ProQOL V) and a demographic and work-related characteristics questionnaire were distributed to 90 health professionals working with migrants and refugees. Results: 25.6% of participants reported high CF risk while 75.7% expressed high to moderate potential for CS. Awareness of the factors associated with CF may help health professionals to prevent or offset the development of this condition. Conclusion: A compassionate organizational culture, clinical supervision and on-going education may protect health professionals working with migrants and refugees from absorbing or internalizing unmanageable emotions which may lead to compassion fatigue and also help them to gain a deeper understanding of their communication and interactions during the emotionally laden moments of trauma care.