Three cells were tested under different conditions to mimic the situation with stacks arranged in gas flow series or parallel. The effects of reactant conversion ratio and inlet gas composition on the cell performance and durability were studied. The cells were operated under −1 A/cm2 at 800 °C for H2O + CO2 co-electrolysis. Flows were adjusted to realize the same overall production of syngas. Detailed electrochemical characterization was performed before, during and after the aging test and microstructural changes after aging were investigated. The results show that a gas-flow series arrangement is advantageous as it leads to reduced cell degradation: Reducing the H2O + CO2 conversion from 56% of a gas flow “parallel” case (Cell P) to 28% in the upstream of the series connected cells (Cell SU) and 39% in the downstream one (Cell SD) reduces the overall cell voltage degradation rate from 372 mV/kh for Cell P to140 mV/kh and 69 mV/kh for Cells SU and SD, respectively. This is tentatively ascribed to the “milder” overall conditions realized in the gas flow series case, where the average as well as maximum polarization (and local current density) is reduced relative to the parallel flow case.