Background: This study examines how loneliness and the body’s stress response system interact to regulate social connections. We suggest that the drive to reconnect signaled by loneliness can be accompanied physiologically by the production of cortisol, which can offer supportive coping resources. Thus, we investigated how loneliness, cortisol levels, and their interaction predicted changes in network connections in a social organization. Participants (n = 193; 53% female) provided friendship network data at two times. At time 1, participants reported on loneliness and donated saliva (later assayed for cortisol). Results revealed that concurrently, lonely individuals reported fewer friendships, whereas over time, they named more friends. These results support the hypothesis that loneliness is a signal to develop connections. We also explored whom lonely individuals befriended over time. Results showed that cortisol significantly moderated the preference for friends with a similar level of loneliness. Specifically, lonely individuals with higher cortisol befriended those who were less lonely over those who were lonelier. Thus, cortisol levels may serve an adaptive function in mobilizing resources to develop connections that fulfill social belongingness needs. Results supported the theorized signaling function of loneliness and revealed that loneliness and the stress response system interact to shape social connections.