Electrochemical sensing is a highly effective technique for rapidly detecting and quantifying the presence of electroactive compounds in solution. However, effective sensing requires the electrode surface to be free of contamination, which makes this technique particularly susceptible to the effects of surface fouling due to the unwanted adhesion of biomolecules. Unfortunately, coating electrodes with antiadhesive molecules typically causes electrical passivation with detrimental effects upon electrochemical processes. Lubricin is a large glycoprotein found in articular joints, which self-assembles on most substrates and exhibits excellent antiadhesive properties. This report finds that lubricin antiadhesive coatings function as a size-selective transport barrier that physically blocks large, fouling molecules (e.g., proteins) while still allowing small molecules to diffuse into, out-of, and within this layer more-or-less unimpeded. The diffuse nature of the lubricin coatings ensures the electrode retains a large, “free” surface area that facilitates efficient charge transfer. Using cyclic voltammetry to measure the oxidation/reduction of a K3[Fe(CN)6] redox couple at a gold electrode (a system particularly susceptible to fouling), this report shows that antiadhesive lubricin brush coatings can be used for highly sensitive amperometric/voltametric detection of small electroactive compounds in highly fouling solutions of proteins and blood plasma with minimal, immediate impact upon the electrochemistry.