It 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.