Background and aimsStudies have consistently demonstrated associations between ultra-processed food and drink (UPFD) consumption and an increased risk of non-communicable diseases. However, there is a lack of data investigating relationships between UPFD intake and intermediate cardiometabolic disease markers. In this study we explored UPFD associations with lipoprotein subclasses. MethodsThis was a cross-sectional study of 1,986 middle- to older-aged men and women randomly selected from a large primary care centre. The percentage contribution of UPFDs to total energy intake was calculated for each participant using the NOVA classification. Lipoprotein particle subclass concentrations and size were determined using nuclear magnetic resonance spectroscopy. Correlation and multivariate-adjusted linear regression analyses were performed to examine UPFD intake relationships with lipoprotein subclasses. ResultsIn fully adjusted regression models, higher UPFD consumption was associated with reduced high-density lipoprotein (HDL) cholesterol concentrations (β = -0.024, p = 0.001), large low-density lipoprotein (LDL) levels (β = -18.645, p = 0.002), total and medium HDL concentrations (β = -0.328, p = 0.012; β = -0.510, p < 0.001), smaller LDL and HDL size (β = -0.026, p = 0.023; β = -0.023, p = 0.024), and increased medium very low-density lipoprotein levels (β = 0.053, p = 0.022), small LDL and HDL concentrations (β = 20.358, p = 0.02; β = 0.336, p = 0.011), and higher lipoprotein insulin resistance scores (β = 0.048, p = 0.012), reflecting greater lipoprotein-related insulin resistance. ConclusionsFindings from this research suggest that increased intake of UPFDs is associated with a more pro-atherogenic, insulin-resistant metabolic profile in middle- to older-aged adults which may be a potential mechanism underlying reported associations between UPFD consumption and chronic disease risk and mortality.