Ion-exchanger based Donnan exclusion membranes (IEDEM) are studied here as separators for counter and pseudo-reference electrodes in bioelectroanalysis. Since the potential across the membrane remains indifferent for a wide range of current densities in contact with electrolyte solutions, IEDEM behave as ideally non-polarizable membranes. Consequently, such membranes may be suitable with counter or reference electrode, depending on the adopted cell configuration (three- or two-electrode system). Four configurations were characterized in order to establish the limitations of commercial anion-exchanging membranes, using chronopotentiometry as readout protocol. Three- and two-electrode configurations with and without membrane exhibited similar characteristics in terms of drift and reproducibility (observed drift and RSD were 0.0007 s1/2 per scan number and 1.71%, respectively). Several currents amplitudes were applied to evaluate the upper current limits for the membranes, which was found at about 10 mA [42.8 mA cm−2]. This value is significantly above those typically used in chronopotentiometric experiments, which involve hundreds of μA. Three different analytes were measured in human whole blood using an IEDEM as a counter electrode. A divalent cation (calcium), a polyion (protamine), and an anion (chloride) were successfully determined in blood and compared to reference methods. Finally, the obtained results suggest that such membranes may be used in bioelectrochemical sensing approaches to replace expensive but less appropriate electrode materials for the measurement in matrices that contain lipids and proteins.