A single-electron transistor (SET) based on cobalt oxide is proposed and implemented for the first time. The SETs were fabricated through nanofabrication process compatible with the CMOS technology. A native cobalt oxide on the surface of the source and drain Co electrodes is utilized to act as a quantum dot (QD) and tunneling junctions. The SET based on CoO exhibits typical single electron transport characteristics. Owing to the high Coulomb blockade energy (180 meV), the Coulomb blockade regions still remain at room temperature (300 K), revealing the atomic scale CoO-based SETs have great potential to operate at room temperature.