The　concept　of　cascade　mechanical　subcooling　is　recommended　to　widen　the　application　of　natural　working　fluid　CO2,　improve　the　efficiency　and　reduce　the　carbon　footprint　of　CO2　refrigeration　system　applied　in　commercial　supermarket.　Three　potential　configurations　for　CO2　system　with　integrated　multi-stage　dedicated　mechanical　subcooling　(MS-DMS)　are　proposed　as　prospect　solutions.　Life　cycle　assessment　is　conducted　from　the　viewpoint　of　exergy,　carbon　footprint　and　cost　performance　for　the　proposed　refrigeration　systems,　and　compared　with　baseline　CO2　booster　refrigeration　system　(BASE)　and　traditional　R404A　system.　8　representative　cities　located　in　diverse　climatic　zones　across　China　are　chosen　as　scenarios　and　discussed　in　detail.　The　results　indicate　the　irreversible　loss　is　efficiently　reduced　with　the　utilization　of　MS-DMS.　The　annual　exergy　efficiency　of　CO2　system　integrated　with　triple-stage　DMS　(TS-DMS)　is　11.92–18.48%　higher　than　BASE.　Life　cycle　climate　performance　(LCCP)　is　reduced　by　6.87%　when　the　TS-DMS　is　employed　in　Haikou　in　contrast　to　BASE　from　the　perspective　of　carbon　emissions.　Additionally,　the　life　cycle　cost　(LCC)　is　remarkably　reduced　by　6.8%　compared　with　BASE.　Consequently,　MS-DMS　CO2　systems　are　more　suitable　for　the　application　in　warm　or　hot　regions　in　contrast　to　BASE　due　to　its　better　emission　reduction　performance　as　well　as　lower　life　cycle　cost.　©　2023　Elsevier　Ltd