The extraction equilibria of copper(II) with Cyanex 301, LIX® 984N, and their mixtures have been investigated. Extractionwas studied as a function of organic phase composition, sulfuric acid concentration, pH, temperature, initial copper concentration, mixing speed, and aqueous/organic volume ratio. Considerable synergistic enhancement has been observed in the extraction of Cu2+ with mixtures of Cyanex 301 and LIX® 984N. The results demonstrate that copper ion is extracted as CuRL2H with synergistic mixture. The thermodynamic parameter, enthalpy change (H) of Cyanex 301, LIX® 984N, and their mixtures have been determined and the endothermic process has been found. The synergistic enhancement factor of copper(II) with mixtures is higher at more acidic solutions, which suggests that it is a promising synergistic extraction system for the separation of copper(II) from more acidic medium. HCl was found to be more efficient for copper stripping from loaded synergistic mixtures.