Objectives <p>In previous studies, several inflammatory biomarkers derived from complete blood cell counts (CBC), such as systemic immune inflammation index (SII), neutrophil-to-lymphocyte ratio (NLR), and non‑high‑density lipoprotein cholesterol to high‑density lipoprotein cholesterol ratio (NHHR) have been identified as predictors of sarcopenia. However, whether Monocyte to High-Density Lipoprotein Cholesterol Ratio (MHR) can predict the development of sarcopenia has not yet been established. The research first attempts to investigate the association between MHR and low muscle mass and to compare the predictive abilities of MHR, SII, NLR, and NHHR for low muscle mass risk.</p> Methods <p>The study comprised 10,321 participants aged 20 years and above from the United States. Multiple logistic regression was performed to explore the association between ln-transformed MHR, SII, NLR, NHHR and low muscle mass. Additionally, AUC values and ROC curves were used to assess the predictive effectiveness of ln MHR and other markers (ln SII, ln NLR, ln NHHR, ln MHR + ln SII, ln MHR + ln NHHR, and ln MHR + ln NLR). The bootstrap estimated 95% Cl was shown with the AUC.</p> Results <p>In the fully adjusted model, ln SII, ln NLR, ln NHHR, ln MHR, ln MHR + ln SII, ln MHR + ln NHHR, and ln MHR + ln NLR were positively associated with low muscle mass (ln SII: OR = 1.59 [1.37–1.84]; ln NLR: OR = 1.35 [1.13–1.60]; ln NHHR: OR = 1.49[1.27–1.75]; ln MHR: OR = 1.98 [1.68–2.33]; ln MHR + ln SII: OR = 1.61 [1.46–1.79]; ln MHR + ln NHHR: OR = 1.42 [1.29–1.56]; ln MHR + ln NLR: OR = 1.58 [1.41–1.78]). Compared to the lowest quartile of ln MHR, higher quartiles were significantly associated with increased odds of low muscle mass (<i>P</i> for trend &lt; 0.0001). In ROC analysis, ln MHR + ln SII had a higher AUC value than other indicators (AUC = 0.608).</p> Conclusion <p>Ln-transformed MHR, SII, NLR, and NHHR were positively associated with low muscle mass. MHR outperforms SII, NLR, and NHHR in predicting sarcopenia.</p>