High-temperature fuel cells are a promising technology due to their high energy efficiency and low environmental impacts compared to conventional engines. Nevertheless, they have a limited lifetime which reduces the use to a few application fields. Among them, Solid Oxide Fuel Cells (SOFCs) have had a recent development at the industrial level in two possible configurations: anode- and electrolyte-supported design. Considering the impossibility to experimentally distinguish the effects of every degradation mechanism on global cell performance, each layer should be tested singularly through ex situ tests and then assembled into a virgin cell to evaluate its role on the whole system by in situ tests. However, this procedure results as quite complex, and some further microstructural changes could occur during cell sintering. In order to overcome these constraints, the proposed approach paired ex situ experimental observations on a single element with modelling results on global SOFC. As a case study, CoMnO/Crofer22 APU and CuMnO/AISI 441 interconnect samples were tested, measuring their resistance variation for some hundreds of hours, followed by a detailed post-mortem microstructural analysis. Based on a previously validated local model, SIMFC (SIMulation of Fuel Cells), the durability of commercial anode- and electrolyte-supported cells was simulated, adding specific degradation functions only for the interconnects in order to highlight their influence on SOFC performance.