Chronic obstructive pulmonary (COPD) patients with mild-moderate daytime hypoxia or normoxia (PaO2 > 60 mmHg) may also have transient oxygen desaturation during sleep. Revisiting literature, the authors consider various features of this condition: the prevalence, causes, diagnostic procedures, symptoms, predisposing factors, consequences and therapy. The conclusion is that isolated nocturnal oxygen desaturation in COPD patients is a pathologic condition not yet sufficiently cleared; it likely represents an intermediate step in the evolution of COPD to overt respiratory failure. Since negative outcomes are possible, nocturnal oxygen desaturation must be early put in evidence and then treated with suitable drugs, correct dietetic regimen, respiratory physiotherapy and nocturnal oxygen-therapy.