To evaluate the effect of nocturnal oxygen therapy (NTOT) and NTOT plus continuous positive pressure ventilation on nocturnal oxyhemoglobin desaturation (NOD) of chronic obstructive pulmonary disease (COPD) patients with acute exacerbation, we monitored 58 COPD patients accompanied with NOD with pulse oximetry day and night. Arterial blood gas analysis was done before and after night sleep. Their PaO2, PaCO2 and basic SpO2 measured in day time were positively related to their nocturnal mean SpO2 (corresponding r = 0.702, 0.613, 0.605, all P < 0.01). Under NTOT, 37 patients showed favorable response showing elevation of the average values of nocturnal mean SpO2 (MSpO2) (P < 0.01), nocturnal minimal SpO2 (mSpO2) (P < 0.01) and decrease of cumulative time of NOD% (CTNOD%) (P < 0.01) in contrast to the values obtained when they breathed in air through whole night. However, another 21 patients failed to respond favorably on NTOT. When they were put on NTOT plus BiPAP ventilation, remarkable improvement of all indices of nocturnal SpO2 was found, and there was also an elevation of daytime PaO2 (P < 0.01) and lowering of PaCO2 (P < 0.01). We conclude that nocturnal oxygen therapy can release NOD of most part of COPD patients, while those who did not respond well to NTOT will improve favorably when continuous positive pressure ventilation was added.