Background: Mounting evidence demonstrates that meditation can lower pain and emotional distress in adults, and more recently, in children. Meditation may be an effective form of emotion regulation in children because it is easily accessible and more easily done across a variety of settings in which toys may not be available, for e.g., settings requiring a “clean” environment (e.g., surgical prep). Further, neuroimaging studies in adults suggest that meditation techniques are neurobiologically distinct from other forms of emotion regulation, such as distraction, that rely on prefrontal control mechanisms, which are underdeveloped in youth. Rather, meditation techniques may not rely on “top-down” prefrontal control and may therefore be utilized across the lifespan. Procedure: We examined neural activation in children with cancer, who experience significant distress. During neuroimaging, children viewed distress-inducing video clips while using martial arts-based meditation (focused attention, mindful acceptance) or non-meditation (distraction) emotion regulation techniques. In a third condition (control), participants passively viewed the video clip. Results: We found that meditation techniques were associated with lower activation in default mode network (DMN) regions, including the medial frontal cortex, precuneus, and posterior cingulate cortex, compared to the control condition. Additionally, we found evidence that meditation techniques may be more effective for modulating DMN activity than distraction. There were no differences in self-reported distress ratings between conditions. Conclusion: Together, these findings suggest that martial arts-based meditation modulates negative self-referential processing associated with the DMN, and may have implications for the management of pediatric pain and negative emotion.