ABSTRACT Objective To evaluate the association between MetS, its components and insulin resistance (IR) with 25(OH)D and hsCRP. The moderator role of 25(OH)D in the association of MetS, its diagnostic components and IR with hsCRP were also explored. Materials and methods A cross-sectional study (2014/2015) with a population-based cohort in Southern Brazil (n = 605). Metabolic syndrome (MetS) diagnosis was defined based on the Joint Interim Statement, while the Homeostasis Model Assessment of insulin resistance (IR) (HOMA-IR) was used for determining IR. Serum concentrations of 25-hydroxy vitamin D [25(OH)D] (ng/mL) and high sensitivity C-reactive protein (hsCRP) (mg/L) were evaluated following standard protocols. 25(OH)D was categorized as sufficiency (>30 ng/mL), insufficiency (20-30 ng/mL) or deficiency (<20 ng/mL) to test its moderator role. Multiple linear regression was used to test the associations. The results were adjusted for possible confounders. Results and discussion Hypertriglyceridemia and IR were associated with lower 25(OH)D concentrations. However, except for systolic blood pressure, other MetS components and IR were associated with higher hsCRP. The association between elevated waist circumference (WC) and hsCRP was moderated by the 25(OH)D concentrations. The hsCRP median concentrations were more than two times higher among those with elevated WC and 25(OH)D insufficiency or deficiency. In this study, inadequate concentrations of 25(OH)D increased the adverse relationship between elevated WC and inflammation. 25(OH)D concentrations could be incorporated into the clinical protocols for monitoring individuals with abdominal obesity to identify those at a higher risk of complications.