Objective: To investigate the correlation between exhaled cyclohexanone concentration and hemodialysis in patients with end-stage renal disease (ESRD), and to explore its potential as a biomarker for assessing recovery, metabolic function, and physical resilience in this population. Methods: A total of 100 patients with ESRD undergoing hemodialysis were recruited for this study. Exhaled breath samples were collected before and after hemodialysis sessions and analyzed for cyclohexanone concentration using gas chromatography-mass spectrometry (GC-MS). Clinical parameters, including urea reduction ratio (URR), serum creatinine levels, and physical performance metrics (e.g., 6-minute walk test), were recorded. Correlations between cyclohexanone concentration, clinical parameters, and physical performance were evaluated using Pearson and multivariate regression analyses. Results: Cyclohexanone concentrations in exhaled breath significantly decreased after hemodialysis (P < 0.05), correlating with improved metabolic clearance as indicated by URR and serum creatinine levels. A significant negative correlation was observed between pre-dialysis cyclohexanone levels and physical performance metrics, such as walking distance and grip strength (P < 0.05). Multivariate regression analysis identified cyclohexanone concentration as an independent predictor of post-dialysis physical resilience and recovery potential. Conclusion: Exhaled cyclohexanone concentration is a promising non-invasive biomarker for monitoring metabolic and physical recovery in patients with ESRD undergoing hemodialysis. Its correlation with clinical and physical performance parameters highlights its potential role in guiding personalized rehabilitation strategies and enhancing physical activity participation. Future research should explore its utility in broader contexts, including sports and physical rehabilitation, to optimize recovery and improve quality of life in patients with chronic kidney disease.