Biofouling deteriorates the performance of sensors operated in biofluids. Protein adsorption is believed to be the first step of biofouling, which also reduces biocompatibility by further inducing cell adhesion, platelet activation, and even inflammation. Current studies of antifouling coatings are focused on polymers and hydrogels, which have succeeded in remaining resistant to protein adsorption, but their application on sensor electrodes is limited due to low conductivity and biocompatibility. Here, we report a spontaneous antibiofouling strategy for sensor electrodes by controlling oxygen vacancies in WO3 nanosheets. Irreversible adsorption of proteins was reduced by 76% in unprocessed human plasma when electrodes were coated with WO3 rich in surface oxygen vacancy. These electrodes maintained 91% of the initial current density after 1 month of incubation in human plasma.