This paper presents a detailed exergy analysis of homogeneous charge compression ignition (HCCI) engines, including a crank-angle resolved breakdown of mixture exergy and exergy destruction. Exergy analysis is applied to a multizone HCCI simulation including detailed chemical kinetics. The HCCI simulation is validated against engine experiments for ethanol-fueled operation. The exergy analysis quantifies the relative importance of different loss mechanisms within HCCI engines over a range of engine operating conditions. Specifically, four loss mechanisms are studied for their relative impact on exergy losses, including (1) the irreversible combustion process (16.4%–21.5%), (2) physical exergy lost to exhaust gases (12.0%–18.7%), (3) heat losses (3.9%–17.1%), and (4) chemical exergy lost to incomplete combustion (4.7%–37.8%). The trends in each loss mechanism are studied in relation to changes in intake pressure, equivalence ratio, and engine speed as these parameters are directly used to vary engine power output. This exergy analysis methodology is proposed as a tool to inform research and design processes, particularly by identifying the relative importance of each loss mechanism in determining engine operating efficiency.