December 2021 - For lithium–sulfur battery commercialization, research at a pouch cell level is essential, as some problems that can be ignored or deemed minimal at a smaller level can have a greater effect on the performance of the larger pouch cell. Herein, the failure mechanisms of Li–S pouch cells are deeply investigated via in operando pressure analysis. It is found that highly porous structures of cathodes/separators and slow electrolyte diffusion through cathodes/separators can both lead to poor initial wetting. Additionally, the Li-metal anode dominates the thickness variation of the whole pouch cell, which is verified by in situ measured pressure variation. Consequently, a real-time approach that combines normalized pressure with differential pressure analysis is proposed and validated to diagnose the morphology evolution of the Li-metal anode. Moreover, applied pressure and porosity/tortuosity ratio of the cathode are both identified as independent factors that influence anode performance. In addition to stabilizing anodes, high pressure is proven to improve the cathode connectivity and avoid cathode cracking over cycling, which improves the possibility of developing cathodes with high sulfur mass loading. This work provides insights into Li–S pouch cell design (e.g., cathode and separator) and highlights pathways to improve cell capacity and cycling performance with applied and monitored pressure.