This paper addresses the challenge of improving the performance of heat pumps (HPs) in cold-climate conditions by applying refrigerant mixtures. The potential benefits of implementing R-32/CO2zeotropic refrigerant mixtures in three different residential air-source HPs for cold climates are studied. The cases considered are conventional residential HP, HP with a variable mixture control system, and HP with a variable compressor speed. The seasonal performance of a heating system with these air-source HPs, supplemented with an auxiliary electric heater, is studied in the cold-climate city of Montreal, Canada. To this aim, a detailed screening HP model previously developed is modified and used. The obtained results highlight the potential HP performance improvement of applying refrigerant mixtures.