A system and method of regenerating a pre-purification vessel is provided that is particularly suitable for pre-purification of a feed air stream in cryogenic air separation unit that uses an oxygen-enriched purge gas stream for regeneration of the pre-purification unit. The disclosed pre-purification systems and methods are configured to remove substantially all of the water, carbon dioxide and other impurities from a feed air stream, optionally including hydrogen and carbon monoxide impurities. The method of regenerating a pre-purification vessel preferably involves regenerating the pre-purification vessel with an oxygen-enriched purge gas after depressurization of the vessel and thereafter partially repressurizing the pre-purification vessel with an auxiliary purge gas thereby diluting the oxygen concentration of the gases contained in the pre-purification vessel and optionally depressurizing the partially repressurized vessel.