Purpose: The purpose of this paper was to examine the relationships between clinical practice stress and burnout, and the mediating role of empathy in nursing students. Methods: A cross-sectional research design was employed. One hundred seventeen nursing students completed questionnaires on clinical practice stress, empathy (perspective-taking, fantasy, empathic concern and personal distress) and burnout in December 2017. IBM SPSS Statistics 23 was used and descriptive statistics, frequency, Pearson correlation coefficient and multiple regression were conducted. Baron & Kenny method and Sobel test were adopted for analysis of the mediation effect (personal distress of empathy). Results: The mean scores of clinical practice stress and burnout were 3.45 and 43.09, and perspective-taking, fantasy, empathic concern and personal distress of empathy were 2.67, 2.42, 2.64 and 2.19, respectively. The highest relationship between clinical practice stress and empathy was personal distress of empathy (r=.32, p<.001). Burnout was positively associated with clinical practice stress and personal distress of empathy (r=.22, p=.015; r=.51, p<.001). Personal distress of empathy demonstrated a complete mediating effect on the relationship between clinical practice stress and burnout (Z=3.22, p=.001). Conclusion: These results showed that decreasing personal distress of empathy is important for nursing students, and may help in reducing clinical practice stress and burnout.