This study tested the foundational affective empathy model, suggesting a sequential affective and cognitive empathy process on compassion fatigue. The sample consisted of 506 Korean adults (253 women, 253 men). The results confirmed that affective empathy was a significant predictor of compassion fatigue increase. In addition, affective empathy was partially mediated by cognitive empathy, and cognitive empathy conversely predicted a significant compassion fatigue decrease. Furthermore, the moderation effect of emotion regulation capability confirmed that the significant increase in compassion fatigue predicted by affective empathy was exacerbated by a moderation effect of emotion regulation capability. Also, analysis of the conditional indirect effect of affective empathy has confirmed that the decrease in compassion fatigue predicted by affective empathy, mediated by cognitive empathy, was reinforced by a moderation effect of emotion regulation capability. Thus, the current study verified the relationship between empathy and compassion fatigue in the foundational affective empathy model. Additionally, the present study confirmed both exacerbating and mitigating effects of emotion regulation on compassion fatigue. •Increase in affective empathy predicts increase in compassion fatigue.•Increase in cognitive empathy predicts decrease in compassion fatigue.•Emotion regulation exacerbates compassion fatigue when used with affective empathy.•Emotion regulation mitigates compassion fatigue when used with cognitive empathy.