BACKGROUND: There is a dearth of population-based studies on the association between the diversity of the oral microbiome and the risk of chronic obstructive pulmonary disease (COPD). The study aims to investigate the association between oral microbiome diversity and COPD. METHODS: In this cross-sectional study, data from the National Health and Nutrition Examination Survey (NHANES 2009-2012) were analyzed. The association between the oral microbiome α-diversity and COPD risk was examined via multivariable logistic regression, with Restricted cubic splines revealing potential non-linear trends. The β-diversity disparities between COPD and non-COPD groups were delineated using Principal Coordinate Analysis (PCoA) and Permutational Multivariate Analysis of Variance (PERMANOVA). RESULTS: A total of 6061 participants were included in this study. For α-diversity, the observed ASVs were significantly associated with COPD risk (OR = 0.964, 95%CI: 0.936-0.993, P = 0.016). Similarly, Faith's phylogenetic Diversity showed a significant association with COPD risk (OR = 0.955, 95%CI: 0.919-0.993, P = 0.020). The Shannon-Weiner index was also associated with COPD risk (OR = 0.829, 95%CI: 0.702-0.981, P = 0.029). For β-diversity, PCoA and PERMANOVA analysis showed statistically significant differences in Bray-Curtis, unweighted, and weighted UniFrac distances (all P <
0.01) between the COPD and non-COPD groups. CONCLUSIONS: Significant differences in oral microbiome α-diversity and β-diversity were found between COPD and non-COPD populations, with α-diversity (observed ASVs, Faith's Phylogenetic Diversity, Shannon-Weiner index) being negatively associated with the risk of COPD.