BackgroundBoth acute exercise and environmental hypoxia may elevate inflammatory cytokines, but the inflammatory response in the hypoxic exercise is remaining unknown.ObjectiveWe performed this systematic review and meta-analysis to examine the effect of exercise in hypoxia on inflammatory cytokines, including IL-6, TNF-α and IL-10.MethodsPubMed, Scopus and Web of Science were searched to identify the original articles that compared the effect of exercise in hypoxia with normoxia on IL-6, TNF-α and IL-10 changes, published up to March 2023. Standardized mean differences and 95% confidence intervals (CIs) were calculated using a random effect model to (1) determine the effect of exercise in hypoxia, (2) determine the effect of exercise in normoxia and (3) compare the effect of exercise in hypoxia with normoxia on IL-6, TNF-α and IL-10 responses.ResultsTwenty-three studies involving 243 healthy, trained and athlete subjects with a mean age range from 19.8 to 41.0 years were included in our meta-analysis. On comparing exercise in hypoxia with normoxia, no differences were found in the response of IL-6 [0.17 (95% CI − 0.08 to 0.43),p= 0.17] and TNF-α [0.17 (95% CI − 0.10 to 0.46),p= 0.21] between the conditions. Exercise in hypoxia significantly increased IL-10 concentration [0.60 (95% CI 0.17 to 1.03),p= 0.006] compared with normoxia. In addition, exercise during both hypoxia and normoxia increased IL-6 and IL-10, whereas TNF-α was increased only in hypoxic exercise condition.ConclusionOverall, exercise in both hypoxia and normoxia increased inflammatory cytokines; however, hypoxic exercise may lead to a greater inflammatory response in adults.Supplementary InformationThe online version contains supplementary material available at 10.1186/s40798-023-00584-6.