In this paper, the ethane oxidative dehydrogenation (ODH) mechanism is thoroughly investigated via isotopic labeling and methanol sorption studies over NiO and highly selective Ni0.85Nb0.15Ox, catalysts. ODH experiments with unlabeled and deuterium labeled ethane demonstrated the existence of strong kinetic isotope effect (KIE) over both NiO and Ni0.85Nb0.15Ox indicating that C-H bond scission is the rate determining step in ethane ODH. Similar KIE values obtained for NiO and Ni0.85Nb0.15Ox mixed oxide indicate that both catalysts share similar active sites for ethane activation. Methanol adsorption/desorption followed by TGA, MS, and in situ DRIFTS showed that pure and Nb-doped nickel oxide surfaces primarily host the same redox active sites that differ in terms of abundance (i.e. surface concentration) and activity. O-2-TPD studies of used catalysts verified the participation of non-stoichiometric oxygen species in the reaction, which proceeds via a redox mechanism. Based on the above, a detailed reaction mechanism is proposed. (C) 2014 Elsevier Inc. All rights reserved.