Chronic Obstructive Pulmonary Disease (COPD) causes significant burden in Australia, affecting 1 in 13 adults ≥ 40 years(1). COPD is driven by local and systemic inflammation, and infectious and immune crosstalk is established between the gut and lungs, known as the gut-lung axis(2). Dietary intake is an important modifiable risk factor as it significantly impacts the composition and diversity of the gut microbiome, both of which influence immune and cardiometabolic systems via the plasma metabolome(3). This study aimed to examine dietary intake in relation to lung function and identify dysregulated metabolic pathways and potential therapeutic targets in people with COPD. Non-smoking adults with (n = 16; 93.75% male, mean age 73.61 years (SD = 6.15)) and without COPD (n = 17; 41.18% male, mean age 68.01 years (SD = 8.35)) completed the Australian Eating Survey food frequency questionnaire(4), spirometry, and blood collection. Nutrient intake data was adjusted for total energy intake, age, sex and BMI. Logistic regressions were performed to assess differences in dietary intake in each group and Spearman’s correlation (Rho) between continuous variables. Polar semi-untargeted metabolomic analysis in plasma was performed by HILIC-LC-Orbitrap-MS (Metabolomics Australia). Data normalisation and analysis was conducted using MetaboAnalyst 6.0 (https://www.metaboanalyst.ca) to produce principal component analysis, partial least squares discriminant analysis, and Fisher’s exact test to analyse pathway analysis (false discovery rate (FDR) q < 0.05). Welch two-sample t-test (p < 0.05) was performed to determine differences in mean metabolite peak intensities between groups. It was observed that people with COPD have lower self-reported intake of fibre (g/day) (odds ratio 0.82 (95% CI: 0.67-0.99), p = 0.043), iron (mg/day) (odds ratio 0.34 (95% CI: 0.12-0.97), p = 0.043), vitamin E (mg/day) (odds ratio 0.45 (95% CI: 0.21-0.98), p = 0.044), and α-tocopherol (mg/day) (odds ratio 0.47 (95% CI: 0.22-0.99), p = 0.047) versus controls. 150 plasma metabolites were detected, and univariate fold-change analysis identified differences in 28 metabolites, including 19 down- and 9 up-regulated metabolites in COPD (versus control). Five of these metabolites are produced by gut microbiota (indoxyl sulfate, 4-hydroxyphenyl-2-propionic acid, nutriacholic acid, pentadecanoic acid and D-lactic acid). Pentadecanoic acid was positively-associated (Rho = 0.42, p = 0.017) and nutriacholic acid was negatively-associated (Rho = –0.48, p = 0.005) with lung function. Pathway analysis revealed that glyoxylate and dicarboxylate metabolism (q = 0.009), arginine biosynthesis (q = 0.009), the citrate cycle (q = 0.019), and alanine, aspartate and glutamine metabolism (q = 0.039) were enriched in COPD versus controls. The plasma metabolome in COPD is altered, with multiple metabolic pathways implicated. The results suggest that systemic metabolic reprogramming exists in COPD, rather than isolated pathway disruptions. These metabolic pathways and metabolites may provide insight into disease mechanisms and potential therapeutic targets for COPD.