Purpose The purpose of this study was to identify the effects of work stress, compassion fatigue and compassion satisfaction on burnout in clinical nurses. Methods The sample consisted of 268 nurses from two general hospitals located in Seoul and Gyunggi province. Data were analyzed using frequencies, percentages, means and standard deviations, t-test, ANOVA, Scheffé, Pearson Correlation and Hierarchial Multiple Regression. Results Compassion fatigue had a significant positive effect on burnout, while Compassion satisfaction had a negative effect on burnout. The explained variance for burnout was 49% and compassion satisfaction was the most significant factor in burnout of nurses. Conclusion The results indicate that the factors influencing nurses' burnout are work stress, compassion fatigue and compassion satisfaction. Therefore strategies to decrease work stress and compassion fatigue and to enhance compassion satisfaction for nurses are needed.