The intracellular response of ultrasmall carbon ring electrodes has been investigated. Adsorption of high molecular weight species (e.g., proteins, lipids, sugars) on the electrode surface appears to result in deterioration of the amperometric signal, making in vivo voltammetric measurements difficult. Assuming a linear dependence between the degree of electrode fouling and the number of scans taken in the neuronal microenvironment, an analytical method based on both pre‐ and postcalibration data is presented to evaluate the response obtained at deteriorating ultrasmall carbon ring electrodes during intracellular voltammetry. Additionally, poly(ester sulfonic acid)‐coated carbon ring electrodes have been used in an attempt to increase selectivity in intracellular voltammetry and to reduce the effects of electrode fouling. In vitro results obtained in solutions of dopamine, dihydroxyphenylacetic acid, and ascorbic acid indicate some exclusion of anionic species from the electrode by the negatively charged polymer film. Moreover, use of polymer‐coated electrodes in vivo result in such a decrease in the percentage of electrode fouling that the degradation of the response is only 45%. This leads to a more reproducible response and better detection limits compared to results from naked electrodes.