Social support and vagal regulatory capacity (VRC), an index of flexible vagal responses during various types of stress, are linked to attenuated stress responding and positive health outcomes. Guided by the polyvagal perspective, we tested whether children's VRC is associated with attenuated sympathetic nervous system (SNS) stress reactivity in socially supportive conditions. Sixty-one 4- to 5-year-old children living in poverty underwent two standardized laboratory stress induction procedures. Cardiac vagal reactivity (respiratory sinus arrhythmia) to a first set of stressors (social, cognitive, physical, and emotional) indexed VRC. During a second set of stressors, participants were randomly assigned to a supportive or nonsupportive social context, and cardiac sympathetic reactivity (preejection period) was assessed. We hypothesized VRC would predict lower SNS stress reactivity, but only in the socially supportive context. Children with high VRC showed attenuated SNS stress reactivity in the socially supportive context compared to children with high VRC in the nonsupportive context and children with low VRC in either context. Individual differences in VRC predict attenuated SNS stress reactivity in socially supportive conditions. Understanding how social support and VRC jointly mitigate SNS stress reactivity may further efforts to prevent negative health outcomes. Implications for biological sensitivity to context and differential susceptibility theories are discussed.