Abstract Performance characteristics due to fouling in a vapor compression cycle with integrated mechanical sub-cooling are investigated for various applications. Considering the first set of refrigerants i.e. R134a, R410A and R407C, from a first law standpoint, the COP indicates that R134a always performs better unless only the evaporator is being fouled. From a second law standpoint, the second-law efficiency indicates that R134a performs the best in all cases. Considering the second set of refrigerants i.e. R717, R404A and R290, the COP indicates that R717 always performs better unless only the evaporator is being fouled; however, the second-law efficiency indicates that R717 performs the best in all cases. Furthermore, the performance degradation due to fouling of the evaporator always has a larger effect on cooling load capacity while the performance degradation of the condenser always has an overall larger effect on the sub-cooler compressor power requirement as well as the COP of the system. In light of the data generated, a new performance degradation law, presented earlier, is shown to be applicable for this system as well that can reduce the amount of experimentation and help predict relevant quantities of the refrigeration system.