Social rejection has been consistently linked to the development of social anxiety. However, mechanisms underlying the relation have been largely unexplored, which presents an obstacle to fully understanding the origins of social anxiety and to the development of effective prevention and treatment strategies. Two studies were conducted to test the hypothesis that the emotion of social pain following rejection promotes the development of social anxiety in subsequent situations. In Study 1, undergraduate participants were exposed to 2 social situations (Cyberball) 2 days apart. Participants who were rejected in the first situation reported higher social anxiety before and during the second situation relative to those who were included. This effect was fully mediated by initial social pain intensity. In Study 2, all participants were initially rejected. Using double-blinded drug administration, participants were randomly assigned to ingest acetaminophen to alleviate the social pain from rejection, or a sugar placebo. As predicted, the acetaminophen group reported lower social anxiety before and during the second situation. Approximately half of the effect was mediated by reduction in social pain. Notably, the immediate effect of acetaminophen was specific to social pain rather than social anxiety. Results were discussed in the context of literature on the etiology of social anxiety and social pain. Future directions were suggested.