This study was primarily conducted to explore the effect of molecular composition of a base oil matrix on the oxidation kinetics and the variation of different thermodynamic parameters during oxidation. Pressurized differential scanning calorimetry was used because the method is fairly straightforward and highly repeatable. NMR-derived structural parameters and chromatographic and mass spectral data were able to explain the variation in the results obtained. Kinetic parameters of various systems were derived based on peak temperature (K) and program rate (beta) relationship. This methodology allowed calculation of the activation energy, rate constant, acid half-life period of the various test samples under study. Variation in the results of the onset temperature (OT) and start temperature (ST) for different base oils are explained in terms of their molecular composition obtained from quantitative FT NMR studies.