Abstract <p>A series of Cu/SiO₂ catalyst precursor were prepared via the impregnation method using fumed silica as the support. The precursor was reduced to be applied to the dehydrogenation of sec-butanol (SBA) to methyl ethyl ketone (MEK). The contents of various copper species in the catalysts were quantitatively analyzed to elucidate the correlation between copper species ratio and catalytic performance. Furthermore, DFT calculations were carried out using both pure Cu⁰ and Cu⁰/Cu⁺ composite models to investigate the reaction mechanism. The results indicate that the reduction conditions significantly influence the composition of copper species and the catalytic behavior. Increasing of reduction temperature and time leads to higher Cu⁰ content, lower Cu⁺ content, lower conversion of sec-butanol, and higher selectivity toward MEK. The highest catalytic performance was achieved when the ratio of Cu⁰ to Cu⁺ approaches 3&#xa0;:&#xa0;1, leading to an MEK yield of 98.2%. DFT calculations reveal that the preferred reaction pathway involves initial O–H bond cleavage to form an alkoxy intermediate, followed by dehydrogenation at the β-carbon (β-C) to produce MEK. The rupture of the O–H bond was identified as the rate-determining step. Compared to the pure Cu⁰ model, the Cu⁰/Cu⁺ model exhibits strong adsorption energies for all the relevant species and lower reaction energy barriers, demonstrating that Cu⁺ species play a promotive role and act synergistically with Cu⁰ to enhance the dehydrogenation process.</p>