This study investigated whether non-exercise-based estimation of cardiorespiratory fitness (eCRF) mediates the association between health-related quality of life (HRQoL) and comorbidities in older Korean adults with diabetes. A total of 1371 Korean adults (56% women) aged 60 years and older with diabetes was drawn from those who participated in the 2008-2011 Korea National Health and Nutrition Examination Surveys IV and V. Data on comorbidities included hypertension, heart disease (acute myocardial infarction or angina), stroke, arthritis, and chronic renal disease. HRQoL was assessed using the EuroQoL group, which consists of a health-status descriptive system and a visual analogue scale. eCRF was determined with sex-specific algorithms. Age, sex, household income, education level, marital status, smoking, alcohol consumption, and regular exercise were additionally measured as covariates. HRQoL found to be inversely associated with number of comorbidities and positively associated with increasing eCRF category (from low to high) in older Korean patients with diabetes. The Sobel mediation test showed a significant indirect effect (Z = -4.632, < 0.001), and the result of a bootstrap procedure corroborated the Sobel test result: a non-zero range in the 95% bias-corrected confidence interval (95% CI -1.104 to -0.453) indicated that eCRF mediates the impact of comorbidities on HRQoL. Overall, the current findings suggest that enhancing CRF can facilitate positive outcomes, including better HRQoL, for patients with diabetes.