Catastrophizing exerts its deleterious effects on pain via multiple pathways, and some researchers have reported that high levels of catastrophizing are associated with enhanced physiological reactivity to painful stimulation. In this project, 42 generally healthy adults underwent a series of psychophysical pain testing procedures assessing responses to noxious mechanical, heat, and cold stimuli. Pain catastrophizing cognitions were assessed prior to and then immediately after the various pain induction procedures. Blood samples were taken at baseline and then at several time points from the end of the procedures to 1h post-testing. Samples were assayed for serum levels of cortisol and interleukin-6 (IL-6). Both cortisol and IL-6 increased from baseline during the post-testing period (p's<.05), with cortisol returning to baseline by 1h post-testing and IL-6 remaining elevated. Pain catastrophizing, measured immediately after the pain procedures, was unrelated to cortisol reactivity, but was strongly related to IL-6 reactivity (p<.01), with higher levels of catastrophizing predicting greater IL-6 reactivity. In multivariate analyses, the relationship between catastrophizing and IL-6 reactivity was independent of pain ratings. Collectively, these findings suggest that cognitive and emotional responses during the experience of pain can shape pro-inflammatory immune system responses to noxious stimulation. This pathway may represent one important mechanism by which catastrophizing and other psychosocial factors shape the experience of both acute and chronic pain in a variety of settings.