Purpose <p>Obstructive sleep apnea (OSA) is a well-established risk factor for diabetes mellitus (DM), with lipid metabolism disorders implicated in its pathogenesis. The aim of this study is to explore the role of remnant cholesterol (RC), a novel lipid parameter with potentially greater predictive value for DM compared to traditional lipids, in the OSA-DM relationship.</p> Methods <p>This study included participants collected between 2000 and 2023 from the Sun Yat-sen Memorial Hospital (SYSMH) and from the National Health and Nutrition Examination Survey (NHANES) datasets for 2005–2008 and 2015–2018. Mediation analyses were conducted to investigate the role of RC in the OSA-DM relationship and to quantify its effect. Restricted cubic spline (RCS) regression was applied to analyze the association between RC and DM among participants with OSA.</p> Results <p>A total of 3,260 participants from the SYSMH dataset and 9,825 from NHANES were analyzed. A positive association was observed between OSA and RC, RC and DM, and OSA and DM. Mediation analysis revealed that RC mediated the OSA-DM relationship with a significant mediation effect of 10.13% (SYSMH) and 10.02% (NHANES) (both <i>P</i> &lt; 0.001). Furthermore, RCS regression analysis demonstrated a positive relationship between RC and DM in patients with OSA across both datasets.</p> Conclusions <p>RC mediates the OSA-DM relationship and is positively associated with DM in patients with OSA. These findings provide novel insights into the pathophysiological mechanisms linking OSA to DM and highlight RC as a potentially valuable biomarker for assessing DM risk in patients with OSA.</p>