Ostracism (i.e., being ignored/ excluded) is a form of social adversity that powerfully impacts health and well-being. While laboratory research indicates that experimentally manipulated experiences of ostracism impact pain, findings have been mixed. Prior investigations have not considered moderating or main effects of individual histories of ostracism, and have been limited in the scope of their pain testing. In this study, participants without current pain reported lifetime experiences of ostracism prior to a laboratory visit where they were randomized to experience either a single episode of ostracism (i.e., acute ostracism) or control condition that was immediately followed by quantitative sensory testing. Results indicate that the experimental effect of a single episode of ostracism on pain ratings, after-sensations, and temporal summation of pain is moderated by lifetime ostracism; no main effects were found. For individuals with histories of more lifetime ostracism, encountering a single episode of ostracism led to greater pain sensitization relative to the control condition, whereas no experimental effect was observed for individuals with little lifetime exposure to ostracism. These findings indicate that acute experiences of ostracism may be accompanied by periods of hyperalgesia for people who are chronically ostracized, implicating ostracism as a potential social moderator of pain sensitization. People who are stigmatized may therefore experience enhanced pain burden with repeated and accumulating experiences of ostracism. Perspective: Results suggest that in the context of accumulated lifetime experiences of ostracism, single experiences of ostracism evoke central sensitization. In this way, ostracism may function to trigger central sensitization and shape socially and societally-determined patterns of pain burden and disparity.Copyright © 2023. Published by Elsevier Inc.