Cytochrome c oxidase (cco) catalyzes the oxygen reduction reaction in most aerobically respiring organisms. Decades of research have uncovered many aspects relating to structure and function of this enzyme. However, the origin of the unusually fast terminal electron transfer step from heme a to heme a(3) in cco has been the subject of intense discussions over recent years. Yet, no satisfactory consensus has been achieved. Carrying out large-scale molecular dynamics simulation of the protein embedded in a solvated membrane, we obtain a reorganization free energy lambda = 0.57 eV. Evaluation of the quantized single-mode rate equation using the experimental rate and the computed reorganization free energy gives a value of 1.5 meV for the average electronic coupling (H-ab) between heme a and heme a(3). Thus, according to our calculations, the nanosecond electron transfer (ET) is due to a small but significant activationbarrier (Delta G double dagger = 0.12 eV) in combination with effective electronic coupling between the two cofactors. The activation free energy is caused predominantly by collective reorganization of protein residues. We show that our results are consistent with the weak temperature dependence observed in experiment if one allows for very minor variations in the donor-acceptor distance as the temperature changes.