This paper seeks to gain a better understanding of the thermal behavior of Li-ion cells using a previously developed two-dimensional, first principles-based thermal-electrochemical modeling approach. The model incorporates the reversible, irreversible, and ohmic heats in the matrix and solution phases, and the temperature dependence of the various transport, kinetic, and mass-transfer parameters based on Arrhenius expressions. Experimental data on the entropic contribution for the manganese oxide spinal and carbon electrodes, recently published in the literature, are also incorporated into the model in order to gauge the importance of this term in the overall heat generation. Simulations were used to estimate the thermal and electrical energy and the active material utilization at various rates in order to understand the effect of temperature on the electrochemistry and vice versa. In addition, the methodology of using experimental data, instead of an electrochemical model, to determine the heat-generation rate is examined by considering the differences between the local and lumped thermal models, and the assumption of using heat generation rate determined at a particular thermal environment under other conditions. Model simulations are used to gain insight into the appropriateness of various approximations in developing comprehensive thermal models for Li-ion cells.