Background: Nurses working in Psychiatric field are exposed to a stressful and emotionally exhausting experience, which results in compassion fatigue. Defense mechanisms, resilience, and compassion satisfaction are all known as facilitators for adaptation and high professional quality of life. This study aimed to clarify the relation between defense mechanisms, resilience, compassion satisfaction, and fatigue among nurses working at El Azazi Mental Health Hospital. This research utilized a descriptive correlational design. Setting/sample: The composed of 85 nurses working at El Azazi Mental Health Hospital in the Al-Sharkia Governorate participated in this study. In this study, four instruments were employed for data collection: 1) nurses demographic data Questionnaire, 2) Defense Style Questionnaire including 40-items, 3) Professional Quality of Life Scale, and 4) Brief Resilience Scale. Results: The nurses' resilience levels and usage of immature defensive mechanisms showed highly significant positive correlation with compassion satisfaction, but with compassion fatigue showed significant negative correlation. Mature defense style predicts burnout and traumatic stress among nurses with a negative predictor on the compassion satisfaction subscale. Furthermore, the neurotic defense style predicts compassion satisfaction while having a negative predictor effect on traumatic and burnout subscales. Conclusions:  All variables were related to one another, as nurses with high compassion satisfaction had high resilience levels and were more likely to use immature defensive mechanisms than mature and neurotic ones. Also, nurses with high compassion fatigue had low levels of resilience and were more likely to use mature and neurotic defensive mechanisms than immature defensive ones.