We explore the neural correlates underlying distress processing in antisocial personality in cocaine-dependent individuals. Twenty-seven abstinent cocaine-dependent individuals took part in script-guided stress imagery in a functional magnetic resonance imaging study. Regional brain activation during stress imagery was compared with a baseline period, for male and female participants separately. Their California Psychological Inventory socialization scores were then correlated in region of interest analysis with corticolimbic brain regions that showed significant activation during stress. The effect size of activity change in the medial prefrontal cortex is associated with lower socialization score (i.e. greater sociopathy) and with the change in heart rate, but only among female participants. These results highlight important sex differences in the association between antisocial personality and distress processing in cocaine-dependent individuals.