Carbon dioxide (CO2, R744) is an environmentally friendly refrigerant, which is widely used in supermarket refrigeration systems located in cold weather sites. Its use at high outdoor temperatures still requires some additional investigations to accomplish performance similar to the one obtained by employing the conventional working fluids. This paper deals with the theoretical comparison in terms of both annual energy consumption and Total Equivalent Warming Impact (TEWI) of different commercial R744 refrigeration cycles operating in five different warm climates. An innovative CO2 direct expansion (DX) configuration, which serves both the medium temperature (MT) load and the low temperature (LT) one, is also considered. Taking into account the running modes of a typical European supermarket and a R404A multiplex configuration as the baseline, the results showed that enhanced R744 refrigeration technologies are capable of dropping the energy consumption and the TEWI by at least 2.8% and 31.1%, respectively.