This communication reports the first electrochemical study of the human P450 2E1 either absorbed or covalently linked to different electrode surfaces. Glassy-carbon and gold electrodes gave reversible electrochemical signals of an active P450 2E1. Molecular modeling of the enzyme helped to rationalize the results. A monolayer coverage was obtained on gold modified with cystamine/maleimide that covalently linked surface accessible cysteines of P450 2E1. The midpoint potential measured for the oriented P450 2E1 was −177 ± 5 mV comparable to that of the Fe^III/Fe^II of other P450 enzymes. The observed electron-transfer rate for this electrode was 10 s^-1. The turnover of the active enzyme was measured with the P450 2E1 specific substrate p-nitrophenol, resulting in a K_M of 130 ± 3 μM and the formation of 2.2 μM of the p-nitrocatechol product upon application of a −300 mV bias.