Methicillin-resistant Staphylococcus aureus (MRSA) nasal colonization is associated with an increased risk of infection disease. Low muscle mass has been linked to higher levels of inflammatory markers and weakened immune response, which may impact the susceptibility to nasal MRSA colonization. The relationship between muscle function and immune response to pathogens may be bidirectional. This study investigates the association between muscle mass and nasal MRSA colonization in adults.The present cross-sectional study utilized data from the National Health and Nutrition Examination Survey (NHANES) conducted between 2001 and 2004. Appendicular skeletal muscle mass (ASM) adjusted by body mass index (BMI) (ASM/BMI) was used to evaluate muscle mass. Multivariate logistic regression, adjusted for demographic and infection factors, was used to analyze the association between muscle mass and nasal colonization by MRSA. A subgroup analysis based on age and gender was performed to assess the impact of muscle mass on nasal MRSA colonization.Nasal MRSA colonization was more prevalent in females, those with smaller household sizes, lower income, lower ASM/BMI, those who had stayed in healthcare facilities in the past 12 months, and individuals with diabetes and smoking habits. After adjusting for confounding factors, a dose-dependent association was found between decreasing quartiles of ASM/BMI and the risk of nasal MRSA colonization (p < 0.05). Additionally, per 1 unit increase in ASM/BMI was related to a 64% lower risk of nasal MRSA colonization.This study suggests a significant negative correlation between ASM/BMI and the risk of nasal MRSA colonization. However, more prospective studies are required to investigate the causal relationship between muscle mass and colonization.Copyright: © 2024 Chen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.