This study presents experiment and surface complexation modeling (SCM) of synthetic calcite zeta potential in brine with mixed potential determining ions (PDI) under various CO2 partial pressures. Such SCM, based on systematic zeta potential measurement in mixed brines (Mg2+, SO42−, Ca2+ and CO32−), is currently not available in the literature and is expected to facilitate understanding of the role of electrostatic forces in calcite wettability alteration. We first use a double layer SCM to model experimental zeta potential measurements and then systematically analyze the contribution of charged surface species. Calcite surface charge is investigated as a function of four PDIs and CO2 partial pressure. We show that our model can accurately predict calcite zeta potential in brine containing a combination of four PDIs and apply it to predict zeta potential in ultra-low and pressurized CO2 environments for potential application in enhanced oil recovery in carbonate reservoirs. Model prediction reveals that calcite surface will be positively charged in all considered brines in pressurized CO2 environment (>1 atm). The calcite zeta potential is sensitive to CO2 partial pressure in the various brine in the order of Na2CO3 > Na2SO4 > NaCl > MgCl2 > CaCl2 (Ionic strength = 0.1 M).