Pleistocene yedoma sediments store large amounts of soil organic matter (SOM) and are vulnerable to permafrost degradation. Here we contribute to our understanding of yedoma SOM dynamics and potential response to thaw, by molecular characterization of samples from a 5.7 m yedoma exposure, as well as upper permafrost samples that were previously incubated, using Thermally assisted Hydrolysis and Methylation (THM-GC-MS). In general, the SOM is derived from aliphatic material (including cutin and suberin), phenols (lignin, sphagnum acid), polysaccharides and N-containing components (largely microbial SOM). Soil organic carbon (SOC) content and molecular SOM composition follow a sawtooth pattern where local maxima in SOC coincide with lignin and aliphatic material that experienced only slight degradation, and minima with degraded plant-derived SOM and microbial tissue, representing a stratified cryopedolith. The SOC-depleted top 0.9 m (active layer and transition zone) is enriched in microbial SOM probably due to recent thawing. Comparison with CO2 respiration rates indicates that SOM of microbial origin (low C/N) is more labile than aliphatic SOM from well-preserved plant tissue (high C/N). However, we argue that the more stable aliphatic SOM in SOC-rich layers might also be vulnerable to decay, which could, due to its abundance in SOC-rich layers, dominate overall Yedoma C losses due to thermal erosion.