Sarcopenia is a geriatric syndrome characterized by progressive loss of muscle mass and function. Heat shock protein (HSP) A12B is essential for angiogenesis and endothelial function. However, the association of HSPA12B levels with sarcopenia remains unclear. A total of 936 community-dwelling elderly people were recruited, and serum HSPA12B was measured by enzyme-linked immunosorbent assay. Appendicular skeletal muscle mass index (ASMI), grip strength, and gait speed were taken to assess sarcopenia. We found that serum HSPA12B levels in patients with sarcopenia (median [interquartile range] = 182.15 [137.58-225.86] ng/mL) were lower than those in elderly people without sarcopenia (228.96 [193.03-292.93] ng/mL, P <
0.001). Receiver operating characteristic curve analysis indicated that the optimal cut-off value of serum HSPA12B level for predicting sarcopenia was 185.50 ng/mL, with a sensitivity of 52.6% and a specificity of 80.8% (area under curve = 0.742, 95% confidence interval [CI] = 0.711-0.772, P <
0.001). Moreover, serum HSPA12B concentration was positively correlated with ASMI (r = 0.354, P <
0.001), grip strength (r = 0.381, P <
0.001), and gait speed (r = 0.169, P <
0.001). Multivariate logistic regression analysis showed that decreased serum HSPA12B levels (<
185.50 ng/mL) were a risk factor for increased risk of sarcopenia (adjusted odds ratio = 4.335, 95% CI = 3.136-5.993, P <
0.001). In addition, serum HSPA12B level was also positively correlated with serum levels of angiogenesis markers, vascular endothelial growth factor (r = 0.080, P = 0.014), and angiopoietin-1 (r = 0.108, P = 0.001). In summary, our results indicate that low serum HSPA12B level is associated with an increased risk of sarcopenia in the elderly, suggesting a potential role of HSPA12B in the development of sarcopenia.