The inevitable defect chemistry seriously affects the properties of the compounds under high-temperature synthesis conditions. Herein, the defect chemistry of layered lithium cobalt oxides (LiCoO2) is investigated based on the first-principles calculations. The results show that point defects have a great influence on the electronic structure of LiCoO2, thereby affecting the electrochemical properties. These findings provide some important information on the electronic structure of LiCoO2 with intrinsic defects, which is an indispensable complement to the experimental study and provides guidance for optimizing the electrochemical performance of LiCoO2.