Background <p>Chronic inflammation is increasingly recognized as a crucial contributor to sarcopenia pathogenesis, but accurate diagnosis remains a challenge.</p> Aim <p>Our study aims to investigate the relationship between sarcopenia and the Systemic Immune-Inflammation Index (SII), a comprehensive indicator of inflammation.</p> Methods <p>This cross-sectional study enrolled 632 patients. All participants underwent a comprehensive geriatric assessment. Sarcopenia was assessed through the evaluation of handgrip strength and calf circumference. To determine the SII, we used the formula: Platelet count (10⁹/mm³)×Neutrophil count (10⁹/mm³) / Lymphocyte count (10⁹/mm³).</p> Results <p>The average age of the participants was 74.8 ± 6.4, and 62.3% (<i>n</i> = 394) were female. Patients were grouped as non-sarcopenic and sarcopenic. The non-sarcopenic group had 536 patients (84.8%), while the sarcopenic group comprised 96 patients (15.2%). Sarcopenic patients showed a higher median SII score than the non-sarcopenic group (<i>p</i> &lt; 0.001). Multivariate logistic regression analysis revealed that the SII score was significantly and independently associated with sarcopenia even after adjusting for potential confounding factors (β = 1.002, 95% CI = 1.001–1.003, <i>p</i> &lt; 0.001). The ROC analysis identified the optimal cut-off for SII in predicting sarcopenia as &gt; 765. At this threshold, the negative predictive values were determined to be 88.1%, with a specificity of 88%.</p> Conclusion <p>SII is significantly associated with sarcopenia in a geriatric outpatient population, and a population-specific SII cut-off may serve as a novel, simple, and practical biomarker for diagnosing sarcopenia.</p>