A method of processing a substance, such as a food item, utilizing high pressure processing includes providing an enclosed environment including the substance and one or more of the following gases: carbon monoxide, carbon dioxide, nitrogen, nitric oxide, nitrous oxide, hydrogen, oxygen, helium, argon, krypton, xenon and neon. The enclosed environment including the substance and at least one gas is subjected to high pressure processing and sealed in a container. The high pressure processing may occur prior to or after sealing the substance in the container. Control of the amount and type of gases in the enclosed environment including the substance enhances the biocidal efficacy of high pressure processing as well as ensuring desirable sensory qualities of the substance during storage.