BACKGROUND: This research aims to investigate the connection between systemic inflammatory response and metabolic syndrome (MetS) across different age groups, with the aim of proposing more targeted recommendations. METHODS: This study enrolled 15 959 adults from the 2001-2018 National Health and Nutrition Examination Survey of whom 6739 were diagnosed with MetS. After dividing the systemic immune-inflammation index (SII) into 4 quartiles, the Kruskal-Wallis test and weighted chi-square test were employed to assess statistical differences. Weighted multivariable logistic regression analysis, subgroup analysis, sensitivity analysis, and restricted cubic spline were employed to examine the relationship between SII and MetS. RESULTS: Our study revealed that SII exhibits a quantitative association with MetS [odds ratio (OR) = 1.56
95% confidence interval (CI): 1.37-1.79
P <
.001]. Elevated SII is an independent risk factor for the 5 components of MetS. Different age groups and alcohol consumption status could modify the connection between SII and MetS. This connection was statistically significant in the 18 to 65 age group but not in the elderly subgroup (OR = 1.08
95% CI, .95-1.23
P = .248). Multiple imputation confirmed the robustness of our results. Moreover, the connection exhibits an inverted U-shaped curve. CONCLUSION: Our research highlights the predictive significance of SII in forecasting the incidence of MetS in young and middle-aged populations. The differences in inflammatory mechanisms across various age groups necessitate further research for exploration.