Despite decades of investigation and successful applications, the underlying mechanisms that cause the increased permeability of the cell membrane are not fully understood. The formation of aqueous pores in the cell membrane throughout application of the pulse is widely acknowledged, however, molecular dynamic simulations [10,11] do not support the long-lasting permeabilization that is found in experiments. [12,13] Chemical changes to the lipid bilayer and embedded proteins have been hypothesized as an additional mechanism that could explain such difference in timescales. [14] For example, oxidative stress caused by reactive oxygen species (ROS) can initiate chemical reactions such as peroxidation of the membrane lipids which affect the cell membrane integrity. [15] Indeed, generation of ROS and lipid peroxidation have been shown to correlate with the intensity, duration, and number of pulses and increased generation of ROS is associated with higher electroporation efficiencies. [16][17][18][19][20] Electrically induced generation of ROS occurs within cells as well as at the electrode site. [17] At sufficiently high voltages, metallic electrodes induce Faradaic currents that are established by electrochemical reactions at the electrodeelectrolyte interface. Besides ROS, such irreversible Faradic processes might result in pH changing species, formation of gas, chloride oxidation products, and electrode dissolution. [21][22][23][24] The nature and produced species of these reactions strongly depend on the electrode material. Aluminum and stainless steel as well as metals which are generally considered inert and chemically stable, such as platinum, platinum alloys, and gold, support electrochemical reactions resulting in a change in the chemical composition of the electrolyte. [25][26][27][28] A particularly interesting material that has yet to be investigated in the context of electropermeabilization, is the conducting polymer PEDOT:PSS (poly(3,4-ethylenedioxythiophene) doped with polystyrene sulfonate). PEDOT:PSS has emerged as a popular material for biomedical devices due to its electrochemical properties, ease of processing, and commercial availability. [29][30][31] PEDOT:PSS-coated electrodes exhibit a large charge injection capacity due to the mixed ionic-electronic conduction which benefits neurostimulation applications. [32] Despite its proven record for biomedical applications, the electrochemistry Electroporation or electropermeabilization occurs when cells are exposed to sufficiently high-pulsed electric fields. This phenomenon is now an important technique to facilitate the transmembrane transport of molecules, however, the role of the electrode material and associated electrochemical events remain unclear. Here, it is shown that electrical stimulation with PEDOT:PSScoated electrodes strongly reduces irreversible electrochemical reactions that otherwise lead to changes in pH and the generation of reactive oxygen species. Coated electrodes exhibit a slightly higher threshold for cell stimulation, however,...