Recent developments in advanced combustion engines have demonstrated the potential increases in efficiency and reductions in emissions through low temperature combustion (LTC). These combustion modes often rely on high exhaust gas recirculation (EGR), early fuel injection systems, and in some cases a combination of fuels with different reactivities. Despite the advantages of LTC, such operations are highly sensitive to the in-cylinder pre-combustion conditions and face significant challenges in multi-cylinder operation due to cylinder-to-cylinder variations of the combustion process. The cause of cylinder-to-cylinder variations is strongly tied to non-uniform trapped mass. In particular, in-cylinder oxygen concentration plays a critical role in the combustion process of each cylinder and can be leveraged to predict combustion characteristics and to develop control algorithms that mitigate cylinder-to-cylinder variation.This paper discusses a control-oriented model for estimating the in-cylinder oxygen mass fraction of each individual cylinder. The method relies on an Arrhenius correlation that establishes a relation between oxygen mass fraction, ignition delay, fuel activation energy, and in-cylinder average temperature and pressure during the ignition delay period. The scope of this study is the investigation of this relation on a single injection diesel fuel combustion in a multi-cylinder engine where the main characteristics of LTC operation, early fuel injection and high EGR, are realized. The model developed in this work accurately estimates the oxygen mass fraction of an individual cylinder in the 20 operating conditions studied with a standard deviation of 0.47% O2.