Although high dietary polyphenol intake is negatively associated with risk of certain inflammation-associated chronic diseases, the underlying mechanisms are not fully understood and few studies have explored this in adolescents. This study aimed to evaluate the association between intakes of total polyphenols, polyphenol classes, and the 10 most commonly consumed individual polyphenols with inflammatory biomarkers in the blood of European adolescents. In the Healthy Lifestyle in Europe by Nutrition in Adolescence (HELENA) Study, 526 adolescents (54% girls; 12.5-17.5 y) had data on inflammatory biomarkers and polyphenol intake from 2 nonconsecutive 24-h recalls via matching with the Phenol-Explorer database. Inflammatory biomarkers in serum were IL-1, IL-2, IL-4, IL-5, IL-6, IL-10, transforming growth factor β1 (TGF-β1), TNF-α, IFN-γ, soluble vascular adhesion molecule 1 (sVCAM-1), soluble intercellular adhesion molecule 1 (sICAM-1), soluble E-selectin (sE-selectin), white blood cells, lymphocytes, T cells, and C-reactive protein. Multilevel linear models were used to test associations of polyphenol intake with a pro/anti-inflammatory biomarker ratio [(zTNF-α + zIL-6 + zIL-1)/3/zIL-10] as well as with separate inflammatory biomarkers, adjusted for sociodemographic variables, diet inflammation index, BMI z score, and serum triglycerides. The pro/anti-inflammatory biomarker ratio was linearly inversely associated with the intake of total polyphenols (β = -0.11, P = 0.040). When other inflammation biomarkers were considered, the serum IL-10 concentration was inversely associated with total polyphenol (β = -0.12, P = 0.017) and flavonoid (β = -0.12, P = 0.013) intakes, findings that were inconsistent with the biomarker ratio results. However, the anti-inflammatory capacity of polyphenols was confirmed by positive associations of IL-4 with phenolic acid (β = 0.09 P = 0.049) and stilbene (β = 0.13, P = 0.019) intakes and the negative association of IL-1, IL-2, and IFN-γ with lignan intake (β = -0.10, P = 0.034; β = -0.09, P = 0.049; β = -0.11, P = 0.023). The negative relation with the overall pro/anti-inflammatory biomarker ratio suggests a potential anti-inflammatory role of high polyphenol intakes among European adolescents. Nevertheless, associations are dependent on polyphenol type and the inflammatory biomarker measured.