Background <p>Body composition has emerged as an important determinant of respiratory health. Compared with traditional adiposity indicators, the muscle-to-fat ratio (MFR) provides a more comprehensive assessment of body composition quality by simultaneously reflecting skeletal muscle and fat mass. However, the associations between MFR and respiratory function, as well as the potential mediating roles of adiposity-related indicators, remain insufficiently explored in healthy young adults.</p> Methods <p>A cross-sectional study was conducted among 461 Chinese medical students. Body composition parameters, including MFR, body mass index (BMI), waist circumference (WC), and fat mass percentage (%FM), were measured using bioelectrical impedance analysis. Respiratory function was assessed using vital capacity (VC) and vital capacity index (VCI). Univariate and multivariable linear regression analyses were performed to examine associations between body composition indicators and respiratory outcomes. Mediation analyses were conducted to evaluate the indirect effects of BMI, WC, and %FM on the association between MFR and respiratory function. Sex-stratified moderated mediation analyses were further performed to investigate potential sex-specific differences. Sensitivity analyses were conducted after excluding participants with extreme values of MFR, BMI, and WC.</p> Results <p>MFR was positively associated with both respiratory outcomes. After adjustment for age, sex, BMI, and WC, MFR remained significantly associated with VCI (β = 0.144, <i>P</i> = 0.022) and VC (β = 0.154, <i>P</i> = 0.004). BMI, WC, and %FM significantly mediated the association between MFR and VCI. Distinct association patterns were observed between VC and VCI: adiposity indicators were positively associated with absolute VC but negatively associated with VCI, suggesting different physiological implications of body-size–dependent and weight-standardized respiratory measures. Moderated mediation analyses indicated significant sex differences, with stronger indirect effects observed among female participants. Sensitivity analyses yielded results consistent with the primary analyses, supporting the robustness of the findings.</p> Conclusions <p>A higher muscle-to-fat ratio was independently associated with more favorable weight-adjusted respiratory function among Chinese medical students. Adiposity-related indicators statistically accounted for part of this association, and the mediating pathways appeared to differ between males and females. The contrasting findings for VC and VCI highlight the importance of considering body-size normalization when evaluating respiratory outcomes. These findings support the value of comprehensive body composition assessment beyond traditional obesity indicators in respiratory health research and underscore the need for future longitudinal studies to clarify the underlying biological mechanisms and temporal relationships.</p>