High-intensity intermittent exercise can acutely alter circulating cytokines, but findings are heterogeneous. The aim was to systematically synthesize acute blood cytokine responses after a single high-intensity intermittent exercise session in humans. PubMed, Scopus, and Web of Science Core Collection, plus reference screening. Eligibility criteria included original human studies measuring serum or plasma cytokines pre-exercise and at least one post-exercise time point after high-intensity intermittent exercise. Sampling was mapped to prespecified recovery windows. Risk of bias was assessed using RoB 2 (randomized trials) and the Joanna Briggs Institute quasi-experimental tool. Narrative synthesis was used. From 2077 records, 45 studies were included. Most protocols used cycling or treadmill modalities, and sampling clustered in the immediate and early recovery windows. Interleukin 6 most consistently increased after exercise, whereas tumor necrosis factor alpha, interleukin 10, and other mediators showed mixed or context-dependent changes. Risk of bias was commonly rated as some concerns, with frequent limitations in pre-analytical control and reporting. Across included studies, high-intensity intermittent exercise tended to elicit a short-lived myokine-dominant inflammatory signal, characterized primarily by an increase in circulating interleukin 6, most often detected in the immediate and early recovery windows. Conflicting findings for tumor necrosis factor alpha, interleukin 10, redox-related outcomes, and less frequently measured mediators were best explained by a small set of dominant moderators: post-exercise sampling window, exercise dose/internal load, participant metabolic and training phenotype, and pre-analytical or assay-related heterogeneity. Registration: Open Science Framework (osf.io/wspr6; 17 February 2026).
