A high performance laccase-based biofuel cell cathode is developed using carbon nanosheets (CNS) as the catalyst support and buckypaper (BP) as the substrate electrode. Compared to multiwalled carbon nanotube (MWNT)-based electrodes, CNS-based electrodes exhibit better electrochemical properties for the oxygen reduction reaction (ORR) under biologically relevant conditions. It is shown that CNSs are conformally coated on the nanotubule bundles within the BP and that laccase is intimately attached to the CNS-BP. Electrochemical characterization is carried out to derive the kinetic parameters of the ORR at the laccase-CNS-BP cathode. The laccase-CNS-BP exhibits a steep ORR cathodic wave with a Tafel slope of 19 mV decade-1. The onset potential obtained for laccase ORR at CNS-BP is 20 mV higher than that of the MWNT-based electrodes, and the laccase-CNS-BP cathode has a higher current density than MWNT electrodes.