Thermodynamics and kinetics of intrinsic point defects in Na2Fe(SO4)2·2H2O, a high-voltage cathode for Na-ion batteries, are studied by means of first-principles density functional theory. Electronic structures of charged defects are calculated to study their influences towards electronic and electrochemical properties as well as to probe hole polaron formation. As defect formation energy strongly depends on atomic chemical potentials, we initiate a systematic approach to determine their valid ranges for the pentrary Na-Fe-S-O-H compound under thermodynamic equilibria and correlate them with approximated pH parameters in solution-based synthesis. Given chemical potential landscape and formation energy, we find that Fe Na 1 + , V Na 1 - , 0 and Na Fe 1 - , 0 are dominant and their concentrations could be manipulated through pH condition and oxygen content in the precursor solution. It is predicted that the channel blockage due to FeNa would appear under strong acidic growth condition but could be diminished under weak acidic condition (4.7 ≤ pH ≤ 5.6) where NaFe facilitates a faster migration between each diffusion channel. Our results do not only explain the origin of intercalation mechanism and improved electronic conduction, but also demonstrates the pH influence towards conductivities in the cathode material.