Lithium–oxygen (Li–O2) battery is considered as one of the most promising technologies among various electrochemical energy systems, since it can offer much higher theoretical energy density than the conventional lithium-ion battery. However, a high voltage gap between charge and discharge significantly limits the round-trip efficiency and cycle stability of Li–O2 batteries. In the present work, mesoporous Co3O4 is simply prepared and studied as a catalyst in Li–O2 cells. The Co3O4 nanoparticles possesses a high specific surface area and a spinel crystalline structure. Cyclic voltammetries demonstrate that mesoporous Co3O4 catalyst enhances the kinetics for either oxygen reduction reaction (ORR) or oxygen evolution reaction (OER). Such excellent catalytic performance of Co3O4 could be associated with its larger surface area and 3D ordered mesoporous structure. The electrode with mesoporous Co3O4 exhibits a higher discharge capacity and lowers the over-potential for discharge process, compared with the pure carbon electrode. In Li–O2 cells, the Co3O4 cathodes show enhanced electrochemical performances, including a high round-trip efficiency and a prolonged cycle life. More than 65 stable cycles are observed with a Co3O4-catalyzed electrode, which could be attributed to the low recharge voltage, at which main side reactions due to decomposition of TEGDME-based electrolyte can be suppressed.