Oxygen induced reactions during the desorption of volatile organic compounds (VOCs) from adsorbents (such as activated carbon) promote heel buildup and reduce the adsorbent’s lifetime. This study aims to improve the understanding of heel build-up mechanisms in the presence of oxygen in the desorption purge gas. Three activated carbons (ACs) and one zeolite adsorbent were exposed to an extreme condition of 1,2,4-trimethylbenzene (TMB) and high oxygen concentration at three temperatures (150, 200, and 250 °C). Thermogravimetric analysis and gas chromatography-mass spectrometry (GC–MS) were used to assess the thermal stability and chemical structure of the formed heel, respectively. Additionally, nitrogen adsorption was performed to evaluate the effect of heel formation on the adsorbent’s pore properties. Increasing the desorption temperature in the presence of oxygen was found to reduce the BET surface area and increase the oxygen-induced reactions on the adsorbents. Among the three tested temperatures, minimum heel formation was obtained at the intermediate temperature, 200 °C. Compared to zeolite, ACs were more susceptible to oxygen induced reactions at elevated temperatures due to their wide pore size distribution. Further analysis using GC–MS revealed that oxygen presence during the desorption process can form a broad range of organic species in terms of molecular weight, chemical structure, and functional group.