Low-grade systemic inflammation is associated with a range of chronic diseases. Diet may modulate inflammation and represents a promising therapeutic target to reduce metabolic dysfunction. To date, no study has examined Healthy Eating Index-2015 (HEI-2015) diet score associations with biomarkers of inflammation. Thus, our objective was to assess relationships between the HEI-2015 score and a range of inflammatory biomarkers in a cross-sectional sample of 1989 men and women aged 46-73 years, to test the hypothesis that better dietary quality would be associated with more favourable circulating levels of inflammatory biomarkers. Pro-inflammatory cytokines, adipocytokines, acute-phase response proteins, coagulation factors and white blood cell counts were determined. Correlation and linear regression analyses were used to test HEI-2015 diet score relationships with biomarker concentrations. Higher dietary quality as determined by the HEI-2015 was associated with lower c-reactive protein (CRP) and interleukin 6 concentrations, white blood cell (WBC) counts and its constituents, adjusting for sex and age. Associations with CRP concentrations and WBC counts persisted in the fully adjusted models. No associations with complement component 3, tumour necrosis factor alpha, adiponectin, leptin, resistin or plasminogen activator inhibitor-1 levels were identified. Our data suggest that dietary quality, determined by the HEI-2015 score, in middle-to-older aged adults is associated with inflammatory biomarkers related to cardiometabolic health.