Objective Social support is associated with better health. This association may be partly mediated through the social regulation of adrenomedullary activity related to poor cardiovascular health and glucocorticoid activity known to inhibit immune functioning. These physiological cascades originate in the hypothalamic areas that are involved in the neural response to threat. The aim of the study investigated whether the down regulation, by social support, of hypothalamic responses to threat is associated with better subjective health. Methods A diverse community sample of seventy-five individuals, aged 23 to 26 years, were recruited from an ongoing longitudinal study. Participants completed the Short Form Health Survey, a well-validated self-report measure used to assess subjective general health. They were scanned, using functional magnetic resonance imaging, during a threat of shock paradigm involving various levels of social support, which was manipulated using handholding from a close relational partner, a stranger, and an alone condition. We focused on a hypothalamic region of interest derived from an independent sample to examine the association between hypothalamic activity and subjective general health. Results Results revealed a significant interaction between handholding condition and self-reported general health (F(2,72) = 3.53, p =.032, partial $η$2 = 0.05). Down regulation of the hypothalamic region of interest during partner handholding corresponded with higher self-ratings of general health (ß =-0.31, p =.007). Conclusions Higher self-ratings of general health correspond with decreased hypothalamic activity during a task that blends threat with supportive handholding. These results suggest that associations between social support and health are partly mediated through the social regulation of hypothalamic sensitivity to threat.