Depression of pyrite in a low-alkaline system has sparked soaring interests for the multi-metal sulfide minerals flotation recently. This study investigates effects of combined depressants (Ca(ClO)₂ and CaO) on pyrite flotation with butyl xanthate (KBX). Micro-flotation experiments indicate that the addition of 200 mg/L combined depressants (a mass ratios of CaO to Ca(ClO)₂ of 2:3) and 1.0×10⁻³ mol/L KBX at pH 9.5 can effectively depresses the flotation of pyrite, and a minimum pyrite recovery rate of 12.5% is obtained. Basic thermodynamic evaluation results confirm the participation of Ca(ClO)2 significantly decrease the negative Gibbs free energies of pyrite oxidation reaction. Besides, the calcium species (Ca(OH)₂, Ca²⁺ and Ca(Cl)₂) will spontaneously transform into CaCO₃, and it is the ultimate dominant calcium species in the CO₃^2- system. Density functional theory (DFT) results indicate that CaCO₃ can chemically adsorb onto the pyrite surface with an adsorption energy of –671.13 kJ/mol. The O1 and Ca atoms mainly contribute to the bonding process and are responsible for the stable adsorption of CaCO₃. ToF-SIMS results provide strong evidence that the combined depressants increase the amount of hydrophilic species and decrease dixanthogen adsorption onto the pyrite surface. The thickness of the whole formed hydrophilic species is approximately 50 nm. Semiquantitative amounts of hydrophilic species follow the order of hydroxy calcium>iron carbonyl>calcium carbonate. Overall, hydrophilic species repulse adsorption of dixanthogen and significantly reduce the flotation performance of pyrite.