There is a growing interest in the clinical phenomenon of compassion fatigue and its impact on healthcare providers; however, its impact on hospice nurses is basically unknown. This study investigated the prevalence and the relationships between nurse characteristics and compassion fatigue risk. It also provided a model for predicting compassion fatigue risk. A non-experimental descriptive design using cross-sectional data and descriptive and inferential statistics was used. Nurses (N = 216) from 22 hospices across the state of Florida participated in the study. Findings revealed that 78% of the sample was at moderate to high risk for compassion fatigue, with approximately 26% in the high-risk category. Trauma, anxiety, life demands, and excessive empathy (leading to blurred professional boundaries) were key determinants of compassion fatigue risk in the multiple regression model that accounted for 91% (P < .001) of the variance in compassion fatigue risk. Knowledge of these variables may help organizations identify nurses at risk and provide interventions and preventions to maintain optimal nursing care.