Periodic spin unrestricted DFT+U calculations joined with atomistic thermodynamics and model catalytic experiments (TPD-O2, 18O2/16O4 exchange, N2O decomposition, CO and CH4 oxidation) were used to study the structure, stability and reactivity of various surface oxygen species and oxygen vacancies, produced under different thermodynamic conditions on the (1 1 1) surface exposed by the cobalt spinel nanooctahedra. We thoroughly analyzed the stability of differently oxygen covered terminations starting from ΘO = 0.86 nm−2 (isolated monoatomic species) up to ΘO = 5.21 nm−2 (full oxygen monolayer). The constructed 3-dimensional thermodynamic (γ, T, pO2) surface redox state diagram revealed that in typical catalytic pressures of O2 (pO2/p° ∼ 0.01– 1) three principal states of the spinel surface, including a region associated with the presence of μ-superoxo CoO3c–O2–CoT3c and metal-oxo CoO3c-O species (T < 450– 500 °C), a bare surface region (450– 500 °C to 550–600 °C), and a region were surface oxygen vacancies appear (T > 600 °C) may be distinguished. This diagram was used for quantitative assignment of the experimental TPD-O2 desorption peaks, and also, for interpretation of the role that various adoxygen and lattice oxygen species play in the investigated model catalytic reactions. It was shown that CO is primarily oxidized by the suprafacial CoO3c-O2-CoT3c diatomic oxygen and/or cobalt-oxo CoO3c-O species, whereas in low temperature activation of CH4 only the CoO3c-O adducts are involved. With the increasing temperature, the suprafacial methane oxidation route gradually changes into the interfacial Mars van Krevelen scheme, and the later pathway is accelerated above 600 °C, due to the onset of oxygen vacancy formation (in line with 18O2/Co316O4 isotopic exchange experiments). In the case of N2O decomposition the reaction occurs preferably on a bare surface, and the favorable thermodynamics provides a steady driving force for efficient removal of the recombined adoxygen intermediates in the form of gaseous O2. The phase diagram of the alterable surface oxygen states on the (1 1 1) termination was compared to the corresponding diagram for the (1 0 0) facet, to explain the nature and differences in catalytic redox behavior of the cobalt spinel nano-octahedra and nano-cubes. This allows also for prediction of oxygen speciation anisotropy on cubo-octahedral nanocrystals at various temperatures.