A case-control study investigated the association between circulating E-selectin, L-selectin, and P-selectin levels and sarcopenia in 325 older adults (261 controls, 64 sarcopenia cases). Sarcopenia was diagnosed according to the Asian Sarcopenia Task Force 2019, and selectin concentrations were measured in serum by ELISA. Serum P-selectin was significantly higher in patients with sarcopenia versus controls (19.76 ± 10.07 ng/ml vs. 13.12 ± 7.39 ng/ml, p < 0.001), whereas E-selectin levels did not differ between groups. P-selectin demonstrated the ability to discriminate sarcopenia with AUROC = 0.693 and an optimal cutoff of 17.28 ng/mL. Participants with high P-selectin (>17.28 ng/ml) were more likely to have sarcopenia (multivariate OR = 4.20, 95% CI: 1.82–9.69, p < 0.001), low appendicular muscle mass (OR = 2.31), and low handgrip strength (OR = 1.64, 95% CI: 1.02–2.63, p = 0.043). Circulating P-selectin is an independent biomarker of sarcopenia that reflects endothelial activation and inflammatory processes associated with muscle wasting.