This paper investigates the effect of the cetane number (CN) of a diesel fuel on the energy balance between a light duty (1.9L) and medium duty (4.5L) diesel engine. The two engines have a similar stroke to bore (S/B) ratio, and all other control parameters including: geometric compression ratio, cylinder number, stroke, and combustion chamber, have been kept the same, meaning that only the displacement changes between the engine platforms. Two Coordinating Research Council (CRC) diesel fuels for advanced combustion engines (FACE) were studied. The two fuels were selected to have a similar distillation profile and aromatic content, but varying CN. The effects on the energy balance of the engines were considered at two operating conditions; a “low load” condition of 1500 rev/min (RPM) and nominally 1.88 bar brake mean effective pressure (BMEP), and a “medium load” condition of 1500 RPM and 5.65 BMEP. Results were recorded at the same crank angle 50% burn (CA50) condition to decouple fuel effects from engine effects. The results show that the CN of the fuel impacts the distribution of supplied fuel energy in both engine systems. At the low load condition, a decrease in the fractional cylinder heat transfer is seen for the medium duty engine as CN increases. In general, the sensitivity of the engines to CN is found to increase as engine load increases. At the medium load condition, the observed differences in the fractional heat transfer are larger, and this is especially true for the medium duty engine. This in turn balances the tradeoff between the changes in mixture temperatures and combustion durations. Moreover, as the CN increases, the energy lost to the exhaust increases for both engines at the medium load condition. This is in contrast to the low load condition, where increasing the CN increases the energy in the exhaust of the medium duty engine, but decreases the energy in the exhaust of the light duty engine. Finally, at the low load condition, a higher CN consistently increases the brake fuel efficiency of both engines. This is in contrast, to the medium load condition, where increasing the CN of the fuel increases the brake fuel efficiency of the light duty engine, but causes a slight decrease in the brake fuel efficiency of the medium duty engine.