In spite of the large quantity of experimental work which deals with the oxidation of thiols by superoxide, the mechanism of this reaction is still controversial. The ab initio molecular orbital calculations reported here predict that the main reaction pathway includes the formation of a three-electron-bonded adduct followed by the elimination of the hydroxide anion giving the sulfinyl radical as the reaction product. The alternative reaction pathway consisting of hydrogen atom transfer from the thiol to the protonated superoxide radical involves a reaction energy barrier which is significantly higher. The difference between the two reaction energy barriers is clearly beyond the expected computational uncertainty. The systematic scanning of the potential energy surface reveals no other competitive reaction pathways. The present results provide a useful basis for the interpretation of the complex experimental data related to thiol oxidation by superoxide radical in a biological environment.