Association between obstructive sleep apnea (OSA) and frailty progression across various stages of cardiovascular-kidney-metabolic (CKM) syndrome. Data processing and analysis were performed using R version 4.4.0. Multivariate logistic regression models were utilized to assess the association between OSA and Frailty Index. The Cox proportional hazards regression model was utilized to examine the relationship between sleep apnea and frailty across various CKM stages. A total of 5961 participants were included in this study. Compared to the non-frail group (Frailty Index ≤0.21), people with sleep apnea and in the advanced stage of CKM are more prone to developing frailty. In Model 3, adjusted for multiple covariates, the rarely OSA group (odds ratio [OR] = 1.71, 95% confidence interval [CI]: 1.17-2.48), occasionally OSA group (OR = 1.81, 95% CI: 1.25-2.61), and frequently OSA group (OR = 3.08, 95% CI: 1.98-4.79) exhibited an average 71%, 81%, and 208% increase in frailty risk, respectively. For patients with OSA, advanced-stage CKM significantly increases the risk of frailty. Simultaneously, after excluding other confounding factors, patients with advanced-stage CKM had a significantly increased risk of all-cause mortality compared with the population with "no OSA + early-stage CKM." OSA (especially frequent OSA) and advanced CKM (including progressive stages) are independent and synergistic risk factors for frailty. CKM progression may amplify the adverse effects of OSA on frailty.