AbstractIt is widely accepted that plasma‐generated energetic and reactive species are responsible for plasma‐induced sterilization; however, how these species act alone or synergistically to deactivate endotoxic biomolecules is not completely understood. Using a vacuum beam system, we study the effects of vacuum ultraviolet (VUV) radiation, oxygen and deuterium radicals on lipid A, the immune‐stimulating region of lipopolysaccharide. VUV‐induced photolysis causes bulk modification of exposed lipid A film up to the penetration depth of VUV photons, ≈200 nm. Although radical‐induced etch yield of lipid A is lower than VUV‐induced photolysis, secondary ion mass spectrometry and human whole blood‐based assay suggest that radicals render a higher degree of modification at the film surface. This study contributes to the fundamental understanding of plasma effects on biomolecules for a better deactivation scheme and applications. magnified image