The thermal oxidation of pentacontane (C50H102), and of the homopolymer polyisoprene, has been investigated using O-17 NMR spectroscopy. By performing the oxidation using O-17-labeled O-2 gas, it is possible to easily identify nonvolatile degradation products, even at relatively low concentrations. It is demonstrated that details of the degradation mechanism can be obtained from analysis of the O-17 NMR spectra as a function of total oxidation. Pentacontane reveals the widest variety of reaction products and exhibits changes in the relative product distributions with increasing O-2 consumption. At low levels of oxygen incorporation, peroxides are the major oxidation product, while at later stages of degradation these species are replaced by increasing concentrations of ketones, alcohols, carboxylic acids, and esters. Analyzing the product distribution can help in identification of the different free-radical decomposition pathways of hydroperoxides, including recombination, proton abstraction, and chain scission, as well as secondary reactions. The O-17 NMR spectra of thermally oxidized polyisoprene reveal fewer degradation functionalities but exhibit an increased complexity in the type of observed degradation species due to structural features such as unsaturation and methyl branching. Alcohols and ethers formed from hydrogen abstraction and free radical termination reactions are the dominant oxidation products. In polyisoprene, the formation of esters and carboxylic acids is relatively minor, distinctly different from the oxidation of pentacontane. An approximately linear increase in these degradation functionalities is observed with increasing oxidation levels. These results demonstrate the promise of O-17 NMR as a new technique for detailed investigation of oxidative polymer degradation.