A heteropolysaccharide possessing strong inhibitory activity against cholesterol esterase, namely PS-A, was isolated from water extracts of Cordyceps sinensis by activity-guided fractionation. The molecular weight of PS-A was estimated as $4.6{ imes}10^5$ Da. Compositional analysis revealed the presence of D-glucose, D-galactose, and D-mannose at a molar ratio of 2:1:1. The $^1H$ and $^{13}C$ nuclear magnetic resonance spectra, correlation spectroscopy, nuclear Overhauser effect spectroscopy, and heteronuclear multiple bond correlations experiment established the structure of PS-A as follows: ${ ightarrow}3){alpha}-D-glcp(1{ ightarrow}3){eta}-D-glcp(1{ ightarrow}3){eta}-D-glcp(1{ ightarrow}$ ${{{{frownatop2}atopuparrow}atop1}atopsmile}$ ${alpha}$-D-manp Results of the in vitro enzyme assay showed strong inhibition of cholesterol esterase by PS-A, with an $IC_{50}$ value of $12.7;{mu}g/mL$, suggesting the possibility of its usefulness as a potential agent for control of hypercholesterolemia.