The cysteine residue oxidation by the superoxide radical in the gas phase and in aqueous solution was studied using the integrated molecular orbital + molecular orbital (IMOMO) method combining the Quadratic Configuration Interaction (QCISD(T)) and density functional (DFT) methods. The molecular environment effects were systematically investigated by considering two alternative directions of attack of superoxide radical on the thiol and two different cysteine residue conformations. It was found that hydrogen bonding and the electrostatic interactions between the superoxide radical and cysteine side chaine significantly affect the reaction energy barrier, as compared to that derived for the simple thiol model methanethiol. Among the two possible reaction channels, that involving the sulfinyl radical formation is predicted to be the dominant channel in aqueous solution. In a highly hydrophobic environment the thiyl radical formation channel becomes the main cysteine oxidation channel.