--- - |2- Intermittent hypoxia (IH), the key property of obstructive sleep apnea, is closely associated with endothelial dysfunction. Endothelial‐cell‐specific molecule‐1 (ESM‐1, Endocan) is a novel, reported molecule linked to endothelial dysfunction. The aim of this study is to evaluate the effect of IH on ESM‐1 expression and the role of ESM‐1 in endothelial dysfunction. ESM‐1 is significantly upregulated by HIF‐1α/vascular endothelial growth factor pathway under IH in endothelial cells, playing a role in enhancing adhesion between monocytes and endothelial cells, which might be a potential target for IH‐induced endothelial dysfunction. Intermittent hypoxia (IH), the key property of obstructive sleep apnea (OSA), is closely associated with endothelial dysfunction. Endothelial‐cell‐specific molecule‐1 (ESM‐1, Endocan) is a novel, reported molecule linked to endothelial dysfunction. The aim of this study is to evaluate the effect of IH on ESM‐1 expression and the role of ESM‐1 in endothelial dysfunction. We found that serum concentration of ESM‐1, inter‐cellular adhesion molecule‐1 (ICAM‐1), and vascular cell adhesion molecule‐1 (VCAM‐1) is significantly higher in patients with OSA than healthy volunteers (p < 0.01). The expression of ESM‐1, hypoxia‐inducible factor‐1 alpha (HIF‐1α), and vascular endothelial growth factor (VEGF) was significantly increased in human umbilical vein endothelial cells (HUVECs) by treated IH in a time‐dependent manner. HIF‐1α short hairpin RNA and vascular endothelial growth factor receptor (VEGFR) inhibitor inhibited the expression of ESM‐1 in HUVECs. ICAM‐1 and VCAM‐1 expressions were significantly enhanced under IH status, accompanied by increased monocyte–endothelial cell adhesion rate ( p < 0.001). Accordingly, ESM‐1 silencing decreased the expression of ICAM‐1 and VCAM‐1 in HUVECs, whereas ESM‐1 treatment significantly enhanced ICAM‐1 expression accompanied by increasing adhesion ability. ESM‐1 is significantly upregulated by the HIF‐1α/VEGF pathway under IH in endothelial cells, playing a critical role in enhancing adhesion between monocytes and endothelial cells, which might be a potential target for IH‐induced endothelial dysfunction. - 'Journal of Cellular Physiology, Volume 234, Issue 2, Page 1512-1521, February 2019. '