Potentiometric redox measurements were made in solutions of increasing biological complexity starting with buffer solutions containing either potassium ferri/ferrocyanide or ascorbic acid and finishing with plasma and blood. When the concentration of ferri/ferrocyanide was high (similar to 0.2 mM), both biofouled planar and nanoporous gold electrodes gave Nernstian slopes of 55-59 mV. However, at or below a critical concentration (<= 0.1 mM), similar to 20% loss in sensitivity was observed at planar gold in contrast to nanoporous gold where Nernstian behavior was retained. For ascorbic acid, a Nernst slope of -41 mV was observed at biofouled nanoporous gold electrodes. In contrast, biofouled planar gold electrodes failed to give any potentiometric redox response. At all concentrations studied, cyclic voltammetric measurements on biofouled electrodes revealed significant impairment of faradaic electroactivity at planar gold electrodes while no impairment was shown at nanoporous gold. These results indicate that nanoporous gold is an ideal electrode material to use when making both potentiometric and cyclic voltammetric measurements, particularly in complex solutions containing relatively low concentrations of redox molecules. As proof of concept, the redox potential of plasma and blood has been measured using nanoporous and planar gold electrodes and their values compared. (C) The Author(s) 2015. Published by ECS. This is an open access article distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives 4.0 License (CC BY-NC-ND, http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reuse, distribution, and reproduction in any medium, provided the original work is not changed in any way and is properly cited. For permission for commercial reuse, please email: [email protected]. All rights reserved.