Although considerable research has shown the importance of social connection for physical health, little is known about the higher-level neurocognitive processes that link experiences of social connection or disconnection with health-relevant physiological responses. Here we review the key physiological systems implicated in the link between social ties and health and the neural mechanisms that may translate social experiences into downstream health-relevant physiological responses. Specifically, we suggest that threats to social connection may tap into the same neural and physiological 'alarm system' that responds to other critical survival threats, such as the threat or experience of physical harm. Similarly, experiences of social connection may tap into basic reward-related mechanisms that have inhibitory relationships with threat-related responding. Indeed, the neurocognitive correlates of social disconnection and connection may be important mediators for understanding the relationships between social ties and health.