The interaction of advanced glycation end products (AGE) and their specific cell-surface receptor (RAGE) has an important role in the pathogenesis of cardiovascular disease and diabetic complications. Two isoforms of C-truncated RAGE, soluble RAGE (sRAGE) and endogenous secretory RAGE (esRAGE), may prevent activation of RAGE signaling by acting as decoys. This study investigated whether serum esRAGE and sRAGE levels are associated with blood pressure in nondiabetic patients with obstructive sleep apnea (OSA). Male nondiabetic patients (n=139) with OSA were enrolled. Serum esRAGE and sRAGE levels were examined using enzyme-linked immunosorbent assay. Three consecutive seated systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were obtained at 5-min intervals in the morning. In univariate analysis, there was a significant correlation between serum esRAGE and SBP or DBP, but not between serum sRAGE and SBP or DBP. Multiple regression analysis showed that SBP was independently associated with waist circumference, HbA1c, minimum SaO2 and serum esRAGE, and that DBP was independently associated with low-density lipoprotein cholesterol, apnea-hypopnea index, serum AGE and body mass index, but not with serum esRAGE. These results indicated that serum esRAGE levels were inversely associated with blood pressure, especially SBP, in male nondiabetic patients with OSA. esRAGE may have a protective role against hypertension in patients with OSA, and it may be a novel biomarker for OSA patients at high risk of developing cardiovascular diseases.