This study builds on our earlier investigation (see Ganesalingam et al., 2006). We showed previously that children with moderate to severe traumatic brain injuries (TBI) had poorer self-regulation and social and behavioral functioning than their uninjured peers and that self-regulation predicted significant variance in parent- and teacher-rated social and behavioral outcomes, regardless of the presence or absence of TBI. In this study, we examine self-regulation as a mediator of the relationship between TBI and the outcomes. Participants included 65 children with moderate to severe TBI and 65 children without TBI matched for age and gender. Participants were between 6 and 11 years of age. Children completed an assessment of cognitive, emotional, and behavioral self-regulation, and social and behavioral functioning. Mediation was assessed using a bootstrapping approach (a relatively novel statistical method for assessing specific indirect effects in models with multiple mediators). Analyses indicated that, after controlling for socioeconomic status (SES), aspects of self-regulation accounted for individual variation in the outcomes, and acted as a significant mediator of the effects of TBI on the outcomes. Self-regulatory deficits may reflect the relative vulnerability of the prefrontal cortex to TBI and may help account for post-injury difficulties in social and behavioral functioning. (JINS, 2007, 13, 298–311.)