The present study was an initial investigation into the neural mechanisms through which mindfulness attenuates the distress of social rejection. The results extend the growing body of research on mindful emotion regulation to show how this quality of mind may foster adaptive regulation of exclusion-related distress. More mindful individuals reported less distress after social exclusion and this relation was mediated by reduced VLPFC activation during that exclusion and showed less connectivity between the VLPFC and distress-generating regions of the dACC and amygdala. Not only do the current findings help to elucidate what underlying neural mechanisms are involved in the link between mindfulness and social distress, but they provide insight into the relation between mindfulness and the neural connectivity among specific brain regions during social rejection. The findings contribute to our understanding of brain function, mindfulness and their role in social rejection and have implications for the broader role of mindfulness in effectively regulating negative emotional experiences.