This study primarily aims to evaluate the cooling and heating characteristics and provide a performance comparison of CO2, R41, and several CO2/R41 blends for applications in automobile air-conditioning and heat pump systems. Experiments were conducted to reveal the effects of the refrigerant charge, compositions, ambient temperatures, and compressor speeds among the trans-critical and subcritical cycles. The performance merits of the environmental friendliness, energy efficiency, and safety of using CO2/R41 blends are emphasized. The results demonstrate that, at an optimum charge amount, the coefficient of performance of pure CO2 in the heating and cooling modes can be improved up to a maximum of 14.5% and 25.7%, respectively, by increasing the R41 mass fraction. The heating and cooling capacities were both decreased with an increasing R41 mass fraction, as the system mass flow rates decreased owing to the reduction in suction density. The overall system operation pressure, gas cooler outlet temperature, and high- and low-side pressure drops in both the heating and cooling modes were reduced significantly when the mass fraction of R41 increased from 0% to 100%. Furthermore, the effect of the CO2 mass fraction on the flammability of CO2/R41 blends was studied to discuss the advantages of its safety application. Finally, based on the experimental data, a correlation of the optimum high-side pressure for the trans-critical CO2/R41 cycle was developed, showing a deviation of 5% from the data.