An efficient and selective four-electron plus four-proton (4e -?4H +) reduction of O 2 to water by decamethylferrocene and trifluoroacetic acid can be catalyzed by a synthetic analog of the heme a 3?Cu B site in cytochrome c oxidase ( 6LFeCu) or its Cu-free version ( 6LFe) in acetone. A detailed mechanistic-kinetic study on the homogeneous catalytic system reveals spectroscopically detectable intermediates and that the rate-determining step changes from the O 2-binding process at 25 °C room temperature (RT) to the O-O bond cleavage of a newly observed Fe III-OOH species at lower temperature (-60 °C). At RT, the rate of O 2-binding to 6LFeCu is significantly faster than that for 6LFe, whereas the rates of the O-O bond cleavage of the Fe III-OOH species observed (-60 ° C) with either the 6LFeCu or 6LFe catalyst are nearly the same. Thus, the role of the Cu ion is to assist the heme and lead to faster O 2-binding at RT. However, the proximate Cu ion has no effect on the O-O bond cleavage of the Fe III-OOH species at low temperature.