In recent years, the application of non-conventional water sources, such as seawater in metal extraction industries located in arid and semi-arid areas have been increased. In this study, the integration of seawater in the solvent extraction of copper hydrometallurgical operation was investigated. Accordingly, two commercial copper extractants, Acorga M5774 and LIX 984N were used in extraction of copper from a sulfate–chloride solution containing seawater. The results showed a higher concentration of copper in the pregnant leach solution (PLS) as a result of using seawater; however, the concentration of Fe and the impurities that are associated with seawater, i.e., Cl, Na, Mg, Ca, K were also increased. The presence of the chloride ion resulted in a higher copper extraction at pH values below 1.5. Synergistic system of LIX 984 N and Acorga M5774 (1:1 vol mixture 15% v/v) was found more efficient in extraction of copper at pH values below 1.5 in comparison to sole LIX 984 N and Acorga M5774. Similarly, the extraction of impurities (Na, Mg, K, and Cl) were observed less when a mixture of extractants were used. The results showed that increasing the chloride concentration had a negative effect on copper extraction as the organic to aqueous ratio was decreased. The copper extraction mechanism was also studied using single LIX 984N, Acorga M5774, and a 1:1 vol mixture of these two extractants at chloride concentrations of 0 and 40 g/L. Increasing the chloride concentration resulted in the involvement of more organic molecules.