Gas exchange impairment is primarily caused by ventilation-perfusion mismatch in chronic obstructive pulmonary disease (COPD), where diffusing capacity of the lungs for carbon monoxide (DLCO) remains the clinical measure. This study investigates whether DLCO: (1) can predict respiratory impairment in COPD, that is, changes in oxygen and carbon dioxide (CO2); (2) is associated with combined risk assessment score for COPD (Global Initiative for Chronic Obstructive Lung Disease (GOLD) score); and (3) is associated with blood glucose and body mass index (BMI). Fifty patients were included retrospectively. DLCO; arterial blood gas at inspired oxygen (FiO2) = 0.21; oxygen saturation (SpO2) at FiO2 = 0.21 (SpO2 (21)) and FiO2 = 0.15 (SpO2 (15)) were registered. Difference between arterial and end-tidal CO2 (ΔCO2) was calculated. COPD severity was stratified according to GOLD score. The association between DLCO, SpO2, ΔCO2, GOLD score, blood glucose, and BMI was investigated. Multiple regression showed association between DLCO and GOLD score, BMI, and glucose level (R (2) = 0.6, p < 0.0001). Linear and multiple regression showed an association between DLCO and SpO2 (21) (R (2) = 0.3, p = 0.001 and p = 0.03, respectively) without contribution from SpO2 (15) or ΔCO2. A stronger association between DLCO and GOLD score than between DLCO and SpO2 could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed. A weaker association is seen between DLCO and SpO2 (21) without contribution from SpO2 (15) and ΔCO2. This could indicate that DLCO is more descriptive of systemic deconditioning than gas exchange in COPD patients. However, further larger studies are needed.