A series of Mn5Co1Ox catalysts calcined at different temperatures in the range of 400–800 °C were synthesized by coprecipitation of manganese and cobalt nitrates and tested in the oxidation of CO. The specific surface area, structure, and chemistry of the catalysts were studied. In addition, the reduction of the catalysts by hydrogen was studied using in situ X-ray diffraction and temperature-programmed reduction techniques. It was found that the low-temperature catalyst calcined at 400 °C displays the best catalytic activity, which is attributed to its high surface area, low-temperature reducibility, and a high surface content of Mn4+. The formation of highly disperse and active CoMnO3 species and excess oxygen in a Mn3−xCoxO4+δ spinel leads to excellent low-temperature redox properties. The elevated temperature calcination results in a decline in the catalytic activity in CO oxidation due to formation of a well crystalline Mn3−xCoxO4 spinel, a decrease in the surface area and reducibility.