Background: Hypoxia can reduce the levels of soluble receptor for advanced glycation end-products (sRAGE), a new anti-infammatory biomarker of COPD. We assessed sRAGE in patients with hypoxia-related diseases such as COPD, OSA and OSA-COPD overlap. Methods: Plasma levels of sRAGE were measured in 317 subjects at baseline (57 heathy nonsmokers [HNS], 84 healthy smokers [HS], 79 OSA, 62 COPD and 35 OSA-COPD overlap patients) and in 294 subjects after one year of follow-up (50 HNS, 74 HS, 77 OSA, 60 COPD and 33 overlap). Results: After adjusting for age, sex, smoking status and body mass index, sRAGE levels showed a reduction in OSA (− 12.5%, p=0.005), COPD (− 14.8%, p<0.001) and OSA-COPD overlap (− 12.3%, p=0.02) compared with HNS. There were no diferences when comparing sRAGE plasma levels between overlap patients and those with OSA or COPD alone. At follow-up, sRAGE levels did not change signifcantly in healthy subjects, COPD and OSA or OSA-COPD overlap nontreated with continuous positive airway pressure (CPAP). Moreover, in patients with OSA and OSA-COPD overlap who were treated with CPAP, sRAGE increased signifcantly. Conclusions: The levels of sRAGE are reduced in COPD and OSA. Treatment with CPAP appears to improve sRAGE levels in patients with OSA who also had COPD.