Solid oxide fuel cell (SOFC) systems can last over five years, making data collection for lifespan predictions time-consuming. Accelerating their degradation is thus essential to advance the development of next fuel cell generations. Accelerated life testing (ALT) reduces the time-to-failure by operating systems outside normal conditions, but it requires a comprehensive understanding of the degradation mechanisms to select proper stressors. Finding critical stressors and understanding their impact on cell aging are also crucial steps in managing and mitigating system degradation. This paper presents an innovative approach to developing ALT protocols for SOFCs through the application of Design of Experiments (DOE) method. A three-parameter two-level full factorial design with a central point is used to investigate the effect of the temperature, and air and fuel humidity as stressors for ALT. Models correlating operating conditions with degradation metrics are developed using an analysis of variance (ANOVA) methodology and their predications compared with three validation tests. The voltage evolution of the twelve 1000 h tests used in this work are presented in Figure 1. All three parameters investigated had a significant impact on the ohmic and polarization degradation rate suggesting that the temperature, and air and fuel humidity are good stressor candidate. Results showed that the effect of a particular stressor on the degradation rate can depend on the value of the other stressors. This emphasizes that the interaction between stressors is significant and should be taken into consideration when developing ALT protocols. Comparison between the model degradation rate predictions and that obtained on three validation tests showed that the simple linear model with interaction used in this work was not sufficient to accurately represent and predict the ohmic and polarization resistance degradation rates. Replicates and additional experiments at different operating conditions should be performed to evaluate the lack-of-fit and test higher order models. A similar data analysis procedure could be performed on results from distribution of relaxation time, equivalent circuit analysis, or microscopic imaging to offer a more detailed overview of the degradation induced by the selected stressors. This work highlights the importance of strategic stressor choice and comprehensive experimental design in defining ALT protocols for SOFCs. Figure 1