The current research provides novel evidence for motivational trade-offs between the two fundamental human goals of pursuing social affiliation and avoiding disease. In Study 1, participants completed a writing prime that manipulated inclusionary status and found that socially excluded participants indicated lower feelings of current disease susceptibility compared with control and socially included participants. In Study 2, participants were included or excluded via Cyberball and then indicated their preferences for symmetrical versus asymmetrical faces. Socially excluded participants displayed lower preferences for symmetrical faces—a cue associated with greater disease resistance. Finally, in Study 3, participants were primed with either disease threat or a general negative affective state and then indicated their current affiliation interest. Activated disease concerns uniquely led participants to display less interest in social affiliation. Taken together, affiliation needs result in disease avoidance down-regulation to aid reaffiliation, whereas disease concerns result in affiliation down-regulation to facilitate pathogen avoidance.