In order to investigate the influence of the dynamic changes in upper airway (UA) resistance in the pathophysiology of noctural hypoventilation in COPD, we compared the ventilatory pattern and UA resistance, measured at baseline and during CO2 rebreathing, in nine normal men and 13 patients with COPD. Measurements were made during wakefulness and during non-REM sleep during a morning nap after a sleep deprivation night. Ventilatory parameters (VE, VT, VT/TI) were calculated from flow measurements using a Fleich no. 3 pneumotachograph connected to a fitting nasal mask. Pharyngeal pressure was measured with a low-bias catheter referenced to the mask pressure. Baseline UA resistances (supraglottic resistance: SGR) values were similar in the two groups. They significantly increased in both groups from wakefulness to sleep. Furthermore, VE and VT/TI were higher in patients with COPD than in normal subjects during wakefulness and during sleep. The slope of the VE/PETCO2 relationship was significantly lower in patients with COPD than in normal subjects (p = 0.0001), without any significant decrease between wakefulness and sleep. SGR systematically decreased during CO2 rebreathing in both groups during wakefulness and during sleep. The slope of SGR/PETCO2 relationship was lower in patients with COPD than in control subjects during sleep and during wakefulness (p = 0.005), whereas the decrease in SGR with increased VE and VT/TI was similar in both groups and not influenced by sleep. We conclude that the impediment in UA resistance behavior in response to a hypercapnic stimulus in patients with COPD is related to the decrease in their ventilatory response.