The selection of refrigerants for ejector refrigeration systems, within the broader discussion concerning refrigerant phase-out, is a cutting-edge and challenging research topic, owing to the multi-scale challenges in ejector performance. Indeed, it is known that the performances of ejector refrigeration systems depend on the local flow phenomena. For this reason, a precise selection of the refrigerant relies on the understanding of the fluid dynamic phenomena at the “componentscale”, and integrate such information within the so-called “system-scale”. This paper contributes to the current discussion proposing a screening of refrigerants based on an integrated Computational Fluid Dynamic (CFD) Lumped Parameter Model (LPM) approach. In this approach, ejector performances for the different refrigerant are obtained by a validated CFD approach, whereas the cycle is modelled by a Lumped Parameter Model. For the different refrigerants, the energy performances of the systems are evaluated and the effects of the “component-scale” on the “system-scale” are analysed.