Background: The influenza vaccine has shown promise as a mild, exogenous inflammatory challenge, but use of this model is limited by lack of knowledge about the timing of the inflammatory response. This study was designed to characterize the time-course of the acute inflammatory response and explore psychological and behavioral predictors of that response. Methods: Twenty-one young, healthy individuals were recruited to receive the annual influenza vaccine. Serial blood samples were collected immediately before, and 24, 48, and 72 h following influenza vaccination. Interleukin (IL)-6 concentrations were assayed at each time-point and psychological and behavioral factors (anxiety and depressive symptoms, sleep disturbance, and childhood adversity) were assessed at baseline. Results: Significant elevations in IL-6 were observed at 24 h post-vaccination (mean increase = 0.70 pg/mL, Cohen’s d = 0.54, p = .018)), with 61.9% of participants exhibiting peak concentrations at that time point, χ2 = 22.54, p
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