Abstract The oxidative degradation of organic matter is a key process in the biogeochemical functioning of the earth system. Quantitative models of organic matter degradation are therefore essential for understanding the chemical state and evolution of the Earth’s near-surface environment, and to forecast the biogeochemical consequences of ongoing regional and global change. The complex nature of biologically produced organic matter represents a major obstacle to the development of such models, however. Here, we compare the energetics of the oxidative degradation of a large number of naturally occurring organic compounds. By relating the Gibbs energies of half reactions describing the complete mineralization of the compounds to their average nominal carbon oxidation state, it becomes possible to estimate the energetic potential of the compounds based on major element (C, H, N, O, P, S) ratios. The new energetic description of organic matter can be combined with bioenergetic theory to rationalize observed patterns in the decomposition of natural organic matter. For example, the persistence of cell membrane derived compounds and complex organics in anoxic settings is consistent with their limited catabolic potential under these environmental conditions. The proposed approach opens the way to include the thermodynamic properties of organic compounds in kinetic models of organic matter degradation.