Glucosamine sulfate (GAS) is a charged monosaccharide molecule that is widely used as a treatment for osteoarthritis, a joint disease related to friction and lubrication of articular cartilage. Using a surface force balance, we examine the effect of GAS on normal and, particularly, on shear (frictional) interactions between surfaces in an aqueous environment coated with small unilamellar vesicles (SUVs), or liposomes, of hydrogenated soy phosphatidylcholine (HSPC). We examine the effect of GAS solution, pure water, and salt solution (0.15 M NaNO3) both inside and outside the vesicles. Cryoscanning electron microscopy shows a closely packed layer of liposomes whose morphology is affected only slightly by GAS. HSPC-SUVs with encapsulated GAS are stable upon shear at high compressions (>100 atm) and provide very good lubrication when immersed both in pure water and physiological-level salt solutions (in the latter case, the liposomes are exceptionally stable and lubricious up to >400 atm). The low friction is attributed to several parameters based on the hydration lubrication mechanism.