There is limited knowledge on the relationship between diffusing capacity of the lung for carbon monoxide (D L CO) and quantitative computed tomography (CT) measures of emphysema and airway wall thickness.What is the relationship between D L CO and the quantitative CT measures of emphysema and airway wall thickness in subjects with and without COPD?We included 288 COPD subjects (70% men) and 425 non-COPD subjects (54% men). All subjects were current or ex-smokers older than 40 years and all subjects underwent spirometry, diffusing capacity tests and CT examination. Quantitative CT measures included % low attenuation areas <−950 HU (%LAA) and standardized airway wall thickness (AWT-Pi10).Multiple linear regression analyses showed significant associations between D L CO and both %LAA and AWT-Pi10 in the COPD group. The adjusted regression coefficients (SE) for D L CO (mmol min −1 kPa −1 ) were −1.15 (0.11) per 10% increase in %LAA and 0.08 (0.03) per 0.1 mm increase in AWT-Pi10, and the models’ adjusted R 2 was 0.65 and 0.49, respectively.CT measured emphysema explains a large fraction of the variation of D L CO among COPD subjects, and more so in men. Airway wall thickness is also significantly associated with D L CO, but explains a much smaller fraction of the variation.