Background During adolescence, peer victimization is a potent type of social stressor that can confer enduring risk for poor mental and physical health. Given recent research implicating inflammation in promoting a variety of serious mental and physical health problems, this study examined the role that peer victimization and cognitive vulnerability (i.e. negative cognitive styles and hopelessness) play in shaping adolescents’ pro‐inflammatory cytokine responses to an acute social stressor. Methods Adolescent girls at risk for psychopathology (n = 157; Mage = 14.73 years; SD = 1.38) were exposed to a laboratory‐based social stressor before and after which we assessed salivary levels of three key pro‐inflammatory cytokines – interleukin‐6 (IL‐6), interleukin‐1β (IL‐1β), and tumor necrosis factor‐α (TNF‐α). Results As hypothesized, adolescents with greater peer victimization exposure exhibited greater increases in IL‐6 and IL1‐β in response to the laboratory‐based social stressor. Moreover, for all three cytokines individually, as well as for a combined latent factor of inflammation, peer victimization predicted enhanced inflammatory responding most strongly for adolescents with high levels of hopelessness. Conclusions The findings reveal a biological pathway by which peer victimization may interact with cognitive vulnerability to influence health in adolescence.