A combined experimental and theoretical study of the effect of the polyatom nature (W or Mo) and/or the location of the Co dopant within the heteropoly compound structure on the aerobic liquid phase oxidation of cyclooctane has been carried out. Compounds monosubstituted with Co, either in the cationic position, i.e., CoHPW(Mo)(12)O-40, or within the Keggin anion, i.e., TBA(4)HPW(Mo)(11)CoO39 (TBA = tetrabutylammonium) were synthesized and their identity confirmed by characterization with XRF, FTIR, and UV-vis. Oxidation of cyclooctane proceeded via autooxidation mechanism. Experimentally observed patterns of the catalytic behavior depended on the polyatom nature (W or Mo) and/or the location of the Co dopant within the heteropoly compound structure. In general, Mo-based catalysts proved more active than their tungsten counterparts, and location of Co within the Keggin unit more beneficial than addition of cobalt as a counter cation. DFT modeling of Co-substituted Keggin anions and calculations of free enthalpy for the elementary steps of key importance for the chain initiation and the chain propagation/branching provided rationale for the observed effects.