Proton exchange membrane water electrolysis (PEMWE) is a key technology for sustainable hydrogen production, yet long-term stability remains a challenge. This study evaluates degradation mechanisms in a 25 cm² catalyst-coated membrane electrolyzer cell using IrO₂/RuO₂ as anodic and Pt-based cathodic electrocatalysts, under both potentiostatic and galvanostatic conditions, and investigates the effect of acid-based regeneration. Under 2.0 V potentiostatic operation, current density declined steadily, particularly in the initial phase, stabilizing at ~204 µA/h·cm². Galvanostatic operation required ~50 mV more to maintain target current, indicating performance loss. Post-immersion in 1 M H₂SO₄, partial performance recovery was observed, but subsequent degradation accelerated to ~860 µA/h·cm², highlighting the regeneration’s limited durability. Electrochemical impedance spectroscopy (EIS) showed faradaic processes degrade earlier and more severely than mass transport, especially at 2.3 V. Increasing ohmic resistance indicated membrane dehydration and loss of interfacial integrity. No fluoride was detected, excluding chemical attack by oxidizing species. X-ray diffraction revealed peak broadening and cathodic Pt disorder, partially reversible upon regeneration. SEM-EDS analysis showed no new elements, suggesting structural reorganization. Loss of (Ru,Ir)O₂ phases at the anode post-regeneration indicated irreversible damage. These results confirm that degradation arises from both kinetic and structural factors, and that regeneration only temporarily mitigates performance losses