Cell surface receptors are the key contributors of macrophage function. Most macrophage cell surface receptors are glycoproteins with sialic acids at the terminal of their glycans. It is well recognized that lipopolysaccharide (LPS) induces cell surface sialylation changes that may in turn contribute to macrophage functions. In addition, cellular mechanics such as elasticity is also a major determinant of macrophage function, which in turn is modulated by LPS. In this report, we characterized the sialylation status of macrophages upon LPS stimulation and assessed the changes in its mechanical properties and function. Specifically, we confirmed that sialylation status is closely related to macrophage biomechanical characteristics (elastic modulus, tether force, tether radius, adhesion force, and membrane tension) and thus directly involved in macrophage function. Further, we modulated macrophage sialylation status by feeding the cell with exogenous free sialic acid (Neu5Ac, Neu5Gc) and sialidase inhibitors, and examined the resulting effects on cellular mechanics and function. A systematic recognition of sialylation status related to cellular mechanics of macrophages will contribute to defining their phenotypes and elucidate macrophage functional diversity. (C) 2019 Elsevier Inc. All rights reserved.