Broader contextMicrobial fuel cells (MFCs), generate electrical power through the anodic oxidation of organic substrates mediated by micro-organisms, while the reduction of the electron acceptor (oxidant) occurs at the cathode. One of the proposed applications of such bio-electrochemical devices is the bio-remediation of wastewater coupled to the production of bio-energy. In order to increase the power output of these fuel cells, work is underway to improve the fuel cell design and the electrode reaction kinetics. At the cathode, oxidants such as potassium permanganate or ferricyanide have been used to boost MFCs power output. From a sustainability point of view however, molecular oxygen is the oxidant of choice since it is freely available and can be reduced to water. In this communication we have considered the linking of an efficient O2-reducing enzymatic cathode to a microbial anode. We found that this combination gives a higher maximum power output compared to the MFC based on ferricyanide at the cathode. We advocate that enzymatic cathodes should be considered to improve the performance of MFCs, but this must be weighed against the advantages/drawbacks of chemical and microbial alternatives for the catalysis of molecular oxygen reduction at the cathode.