Hypercapnia is common in chronic respiratory failure (IRCO), and may be further increased in a significant way by oxygen therapy, used for severe hypoxaemia in acute exacerbations. The determinants of PaCO2 are metabolic (hence importance of alkalosis) and ventilatory. In chronic airflow obstruction, CO2 production and ventilation are normal; thus the factor responsible for hypercapnia is essentially the fraction of total ventilation lost in the anatomical and alveolar (VD/VT ratio) dead space, whose effect on PaCO2 is all the more marked on account of the high starting point. From the time of administering pure oxygen hypercapnia is only weakly linked to changes in total ventilation (which, after a few minutes returns to its initial level) and only slightly to the correction of hypoxaemia and desaturation (Haldane effect). On the other hand, the ventilation-perfusion ratios are altered, as evidenced by increased VD/VT ratios. The exact mechanisms are ill understood, but one could consider the worsening venous admixture effect by the reduction of hypoxic vasoconstriction and micro-atelectasis in the poorly ventilated zones, as well as the rise in the anatomical dead space (broncho-dilatation) and alveolar dead space (redistribution of ventilation to poorly perfused zones). In comparison with standard ideas, the genesis of hypercapnia from oxygen therapy depends more on an AIR/BLOOD mis-match, than on the suppression of the hypoxic ventilatory stimulus.