The enthalpies of formation are a critical fundamental parameter for the combustion modelling. The enthalpies of formation of the species of the high temperature combustion mechanism of the lignocellulosic biofuel, ethyl levulinate are determined by a number of methodologies. Chemical group additivity, atomization and isodesmic worked reactions are employed with total reaction energies computed from theory with the CBS-QB3, CBS-APNO, and G4MP2 methodologies. These calculations reveal that significant differences as high as 6.2 kcal/mol can be found between each method for the large oxygenated hydrocarbons that were tested. It is found that there is a lack of standard reference enthalpies of formation for liquid-fuel size oxygenated hydrocarbons for both molecules and radicals. In their absence, a benchmarking of the computational methodologies employed in this study to values available in the Active Thermochemical Tables for smaller oxygenated species is performed. The results show that the atomization methods performed at each separate theoretical method show mean absolute deviations against the benchmarking data set of between 0.4–0.7 kcal/mol for radicals, and 0.6–1.9 kcal/mol for molecules. By combining the data obtained with each individual method by unweighted averaging, mean absolute deviations of 0.3 and 0.5 kcal/mol for radicals and molecules can respectively result. However, the computed enthalpies of formation via the atomization procedure of larger species, of the ethyl levulinate system show variations of between 4.3–6.2 kcal/mol for molecules and 0.9–3.4 kcal/mol for radicals. As the values generated by the isodesmic reaction procedure show lower variations of 0.5–0.8 kcal/mol for radicals and 2.3–3.8 kcal/mol for molecules. Consequently, in the absence of more appropriate reference data to benchmark computational methodologies, this study recommends the use of isodesmic reactions executed at multiple theoretical methods for the determination of enthalpies of formation.