Extremely high energy density and environment friendly reaction make Li-O2 batteries a promising energy storage system. In order to improve the energy efficiency and cycle life of Li-O2 battery, spinel mesoporous CuCo2O4 was successfully synthesized by a facile hydrothermal method and investigated in Li-O2 batteries. The electrochemical measurements show that mesoporous CuCo2O4 possess higher oxygen reduction and oxygen evolution activity than bulk CuCo2O4 both in alkaline and non-aqueous solution. Owing to the inherent catalytic activity, high conductivity and facile mass transfer of mesoporous CuCo2O4, Li-O2 battery shows enhanced electrochemical performances, including much lower charge overpotential and a high capacity up to 5288 mAh g−1. When restricting the discharge capacity at 500 mAh g−1, it could operate over 80 cycles and exhibit superior cycle stability. These results indicate that mesoporous CuCo2O4 nanoparticles are appropriate bifunctional catalysts for Li-O2 batteries.