The design of innovative combustion processes relies on a comprehensive understanding of biodiesel oxidation kinetics. The present study aims at unraveling the reaction mechanism involved in the epoxidation of a realistic biodiesel surrogate, methyl trans-3-hexenoate, by hydroperoxy radicals using a bottom-up theoretical kinetics methodology. The obtained rate constants are in good agreement with experimental data for alkene epoxidation by HO2. The impact of temperature and pressure on epoxidation pathways involving H-bonded and non-H-bonded conformers was assessed. The obtained rate constant was finally implemented into a state-of-the-art detailed combustion mechanism, resulting in fairly good agreement with engine experiments.