Natural refrigerants, which naturally occur in the environment and are non-synthetics substances, have been used as cooling fluids in refrigerator systems for more than hundred years. However, due to safety and performance issues the chemical refrigerant substances replaced them. Over the last two decades, due to the component availability on the market natural refrigerants are getting back all the attention to re-establish their use into applications where previously HFCs were the preferred and only options. Natural refrigerant substances include CO2 (R744,) ammonia (R717) and hydrocarbons. Due to the limitation on refrigerant charge capacity for hydrocarbon systems, ammonia and CO2 are promising alternatives for food retail centralised refrigeration systems. Both ammonia and carbon dioxide have superior thermodynamic properties. On the other hand, the high toxicity of ammonia and the very high operating pressure of carbon dioxide create barriers on the system applications. A large amount of ammonia is prohibited from the sales area of food retail shops. Moreover, carbon dioxide is less efficiency comparing to HFCs installations for warm climate applications. The combination of the two refrigerants in a cascade configuration, where the ammonia side is located far away from the sales area and the subcritical operation of the carbon dioxide without effect from external ambient conditions, may lead to high system efficiencies. In this paper, a thermodynamic analysis on the performance of an R717/R744 cascade refrigeration system is discussed. The cascade configuration consists of the R717 side, the cascade heat exchanger, an R744 liquid receiver, medium and low direct expansion load, a low-temperature compressor and medium-temperature compressor. Modelling results show that the coefficient of performance of the analysed cascade refrigeration system decreased from 2.20 to 1.57 when the ambient temperature varied from 7 ºC to 40 ºC. In addition, the second law efficiency of the analysed cascade refrigeration system varied from 0.499 to a maximum of 0.547 between ambient temperatures of 7 and 31 ºC, respectively. Finally, the amount of exergy destruction in the condenser, MT evaporator, cascade exchanger and the R717 compressor of the analysed system accounts for a large percentage in total exergy destruction.