The aim of this study was to evaluate whether a short therapy cycle of oral methylprednisolone plus conventional therapy might improve isolated nocturnal hypoxemia evidenced through pulse-oxymetry in 28 patients (19 M/9 F; mean age 71 +/- 8.31) with stable moderate to severe COPD (average FEV1 of 43.33 +/- 9.38 of theoretical) and daytime PaO2 > 60 mmHg. All patients showed oxygen desaturation during the night and apnoea/hypoapnoea index < or = 10, measured by means of a nocturnal polysomnography and were successfully on conventional treatment for COPD. The patients were randomly divided into two groups: 14 (steroid group) were administered methylprednisolone for three weeks at progressively decreasing doses (16 mg/die for the first 7 days, then 8 mg die for another 7 days, and finally 4 mg die for another 7 days) plus conventional therapy (bronchodilators and inhaled corticosteroids). The remaining 14 patients (control group) instead were on conventional therapy only. After 3 weeks for the steroid group, but no for the control group, was improved next parameters (p < 0.0001): VC (L) dropped from 2.53 +/- 0.85 measured at baseline to 2.82 +/- 0.84, FEV1 dropped from 1.07 +/- 0.31 L to 1.23 +/- 0.31 L, the IC dropped from 1.71 +/- 0.48 to 2 +/- 0.37 L, the average nocturnal SpO2% from 90.4 +/- 1.79 to 92.3 +/- 1.72 and the Nocturnal Time % of SpO2 < 90% went from 31.19 +/- 18.12 to 10.88 +/- 11.56 after 3 weeks of therapy. Also dyspnoea, sleep duration and mean heart rate significantly improved (p < 0.0001). There was also a significant correlation between average increase in mean nocturnal SpO2% and in Lowest SpO2% and the variation in inspiratory capacity (IC) and in Sleep Duration % in the steroid group (p < 0.0001). In conclusion, methylprednisolone in combination with conventional medical therapy not only improved lung function values but also mean nocturnal oxyhemoglobin saturation and sleep duration in clinically stabilized COPD patients who experience nocturnal oxyhemoglobin desaturation.