Prior research has documented that mindfulness is negatively associated with aggressive behaviors. Recently, studies have examined mediating psychological constructs that account for the relationships between mindfulness and cyberbullying perpetration. The purpose of the current study was to examine the longitudinal relationship between mindfulness and cyberbullying behaviors through the mediating variables of self-esteem and empathy. This study used a two-wave longitudinal design. The final sample consisted of 661 Chinese junior high school students. Participants completed four self-report questionnaires including mindfulness, self-esteem, empathy, and cyberbullying perpetration. Structural equation modeling revealed that mindfulness was significantly related to cyberbullying perpetration over time. Self-esteem and empathy significantly mediated the relationship between mindfulness and cyberbullying. Future research may focus on the potential mechanisms linking mindfulness and other protective factors with cyberbullying perpetration to facilitate the development and use of cyberbullying interventions.