Differential electrochemical mass spectrometry (DEMS) involves applying a potential across an electrochemical cell and measuring the resulting current while concurrently analyzing gas products with a mass spectrometer. We used DEMS to investigate the mechanism of carbon support corrosion (CSC) in-situ at the cathode of proton exchange membrane fuel cell (PEMFC). The cathode exhaust gases were sampled with a Hiden Analytical QIC-20 mass spectrometer. The spectra of gases were correlated in our laboratory for the first time to characterize most reactions that happen at the cathode in a real PEMFC. Moreover, the sensitivity and resolution of DEMS were improved significantly to enable study of a 5 cm2 membrane electrode assembly (MEA), which makes it very convenient for researchers to compare different catalysts in PEMFC. To further understand the mechanism of CSC, oxygen was isotopically labeled by replacing regular water with oxygen-18 (18O) enriched water (H218O, 98%) in DEMS. Among many surprising results, we showed that water – not oxygen – was the main reaction intermediate in CSC. Knowledge of the CSC mechanism disclosed in our study will boost the design of new carbon supported catalysts for PEMFC with longer lifetime.