Arterial oxyhemoglobin saturation (SaO2) falls to a variable extent during sleep in patients with COPD. These nocturnal falls in SaO2 may contribute to the development of pulmonary hypertension, nocturnal cardiac arrhythmias, and death during sleep. In order to determine which physiologic factors measured during wakefulness might contribute to the development of nocturnal hypoxemia, we performed multiple stepwise linear regression analyses in 48 patients with stable COPD with mean and lowest nocturnal SaO2 as dependent variables. It was concluded that the two chief variables, measured while awake, which are associated with alterations in nocturnal oxygenation in patients with COPD are baseline awake SaO2 and PaCO2. Hypercapnia appears to be a risk factor for the development of nocturnal hypoxemia in patients who are normoxic while awake.