As an oxygen reduction reaction (ORR) catalyst, the activity in acid medium of nitrogen and sulphur co-doped graphene with carbon defect (V-N,S-gra) is investigated via density functional theory (DFT), including the activity sites, the reaction pathways as well as free energy diagrams. Based on the spin-polarized calculations, six kinds of O-2 adsorption configurations are found and the reaction sites are all carbon atoms adjacent to the dopants. However, they are physisorption in the neighboring carbon of nitrogen, unlikely to initialize the ORR process. Otherwise, if the adsorption sites are in the adjacent carbon of sulphur, the catalyst activity is associated with the adsorption energy, that is, we find a best ORR pathway with a gentle adsorption (-0.03eV). An energy barrier of 0.82eV is found in this favorable process in which the adsorbed O-2 molecular is prone to be hydrogenated continuously to give rise to H2O molecular, promising a four-electron pathway. On the other hand, in the O-2 strongly adsorbed configurations, the intermediate *OH is not easily to be hydrogenated in the final step. At last, the effect of electrode potential is simulated and for the best reaction pathway all the elemental reactions are downhill until the potential is as large as 0.31eV. (C) 2019 The Electrochemical Society.