Background <p>Sarcopenia, characterized by the progressive loss of muscle mass and function, is increasingly prevalent among the elderly in China and globally. Emerging evidence suggests that short-chain fatty acids, key metabolites produced by gut microbiota, may influence muscle health. This study aimed to investigate the association between serum short-chain fatty acids and sarcopenia in elderly Chinese women, and to explore potential metabolic biomarkers using a targeted metabolomics approach.</p> Methods <p>A case–control study was conducted involving 100 community-dwelling women aged 65 to 75&#xa0;years in Shanghai, with 50 diagnosed with sarcopenia and 50 age-matched healthy controls. Sarcopenia was defined according to the Asian Working Group for Sarcopenia 2019 criteria. Fasting blood samples were collected, and serum short-chain fatty acid levels were measured using Gas Chromatography-Mass Spectrometry. Dietary intake and demographic data were obtained through structured questionnaires and food frequency assessments. Statistical analyses, including independent sample t-tests and partial correlation analysis, were performed using SPSS version 21.0. Metabolic pathway enrichment was analyzed using MetaboAnalyst.</p> Results <p>Compared to the control group, the sarcopenia group exhibited significantly lower serum levels of propionic acid (<i>P</i> = 0.004) and isovaleric acid (<i>P</i> = 0.001). Pathway analysis identified 19 significantly enriched metabolic pathways, three of which, carbohydrate digestion and absorption, protein digestion and absorption, and degradation of aromatic compounds, were highly associated with propionic and isovaleric acids. Dietary assessment revealed that individuals with sarcopenia had lower intake of energy, total protein, and high-quality protein, but higher sodium intake (all <i>P</i> &lt; 0.05).</p> Conclusions <p>Altered profiles of serum short-chain fatty acids, particularly reduced propionic acid and isovaleric acid, are associated with sarcopenia in elderly women. These metabolites may serve as potential biomarkers for early identification and risk assessment. The findings highlight the relevance of gut microbiota-derived metabolites and dietary factors in sarcopenia pathophysiology and support future development of nutritional and metabolic interventions for prevention.</p> Trial registration <p>The trial protocol was filed with the Chinese Clinical Trial Registry (registration number ChiCTR2100048874) on July 19, 2021.</p>