Currently, extensive research exists on the activation mechanisms of sphalerite, yet there is a notable absence of studies on the mechanisms behind the activation of depressed sphalerite. This paper investigates the mechanism through which moderate or excessive copper ions activate depressed sphalerite under conditions (pH 9–10) of moderate alkalinity, employing a comprehensive approach that includes pure mineral flotation experiments, contact angle measurements, FESEM-EDS, XPS, and density functional theory simulations.The results from pure mineral flotation experiments reveal that, at a copper ion concentration of 1 × 10−4 mol/L, sphalerite, previously depressed by zinc sulfate, is activated by copper ions, achieving a recovery rate of 91.46 % with butyl xanthate as the collector. However, when more cooper ions are added, the recovery of sphalerite decreases. Contact angle measurements and FESEM-EDS data indicate that under conditions of moderate alkalinity, zinc sulfate undergoes hydrolysis to form hydrophilic colloidal substances (hydroxylated zinc) that adhere to the surface of sphalerite, rendering it hydrophilic and thereby depressed. Following the introduction of copper ions, a dense striated material forms on the surface of sphalerite previously inhibited by zinc sulfate, enhancing its hydrophobicity, but if more copper ions were added, the hydrophobicity of activated sphalerite will be weakened. XPS findings further suggest that activated sphalerite by copper is capable of forming polysulfides, which then act on the sphalerite. DFT simulations verify that under moderate alkalinity conditions, copper ions first undergo a hydroxylation reaction in the solution before adsorbing or precipitating on the mineral surface as hydroxylated substances, which subsequently interact with sulfur on the surface of sphalerite. The analysis of the density of states indicates that following the addition of butyl xanthate, the strongest 3p orbital electron peak of the sulfur atom bound to butyl xanthate and the strongest 3d orbital electron peak of zinc are at distinct energy levels, suggesting that the overlap of the electronic density of states is minimal, indicating a weak and unstable interaction between the sulfur and zinc atoms bonded with butyl xanthate. Conversely, the strongest 3p orbital electron peak of the sulfur atom bonded with butyl xanthate overlaps with the strongest 3d orbital electron peak of copper and is positioned near the Fermi level, signifying a strong reactivity and more stable interaction between the sulfur and copper atoms.