Periodic spin unrestricted DFT-PW91+U calculations together with ab initio thermodynamic modeling were used to study the structure, defects, and stability of different terminations of the (100) surface of cobalt spinel under various redox conditions imposed by different oxygen partial pressure and temperature. Three terminations containing under-stoichiometric (100)-O, stoichiometric (100)-S, and overstoichiometric (100)-R amount of cobalt ions were analyzed, and their atomic and defect structure, reconstruction, and stability were elucidated. For the most stable (100)-S and (100)-O facets, formation of cationic and anionic vacancies was examined, and a surface redox state diagram of possible spinel (100) terminations in the stoichiometry range from Co2.75O4 to Co3O3.75 was constructed and discussed in detail. The results revealed that the bare (100)-S surface is the most stable at temperatures and pressures of typical catalytic processes (T ∼ 200 °C to ∼500 °C, pO2/p° ∼ 0.001 to ∼1). In more reducing conditions (T > 600 °C and pO2/p° < 0.0001), the (100)-S facet is readily reduced by formation of oxygen vacancies, whereas in the oxidizing conditions (T < 200 °C and pO2/p° > 10), coexistence of (100)-S and (100)-O terminations was revealed. Formation of the oxygen vacancies involves reduction of the octahedral trivalent cobalt and is accompanied by migration of the divalent tetrahedral cobalt into empty, interstitial octahedral positions. It was also found that the constituent octahedral Co cation proximal to the interstitial cobalt adopts a low spin configuration in contrast to the distal one that preserves its surface high spin state. In the case of the Co depleted surfaces, the octahedral vacancies are thermodynamically disfavored with respect to the tetrahedral ones in the whole range of the examined T and pO2 values. The obtained theoretical results, supported by TPD-O2 and TG experiments, show that the octahedral cobalt ions are directly involved in the redox processes of Co3O4.