Reverse Electrodialysis is today recognized as one of the most promising technology to harvest Salinity Gradient Power (SGP-RE). However, the effectiveness of SGP-RE in real practice is still not clearly defined due to the lack of specific studies in literature, being in large part limited to investigations on pure NaCl solutions. In this work we experimentally investigated the effect of Mg2+, the most abundant cation in natural water after Na+, on SGP-RE performance by power measurements on a lab-scale stack prototype. Maximum power density ranged from 1.06 W/m2MP (MP: membrane pair) - generated when feeding SGP-RE prototype with 0.5 molal//4 molal NaCl, to 0.06 W/m2MP - measured when using 0.5 molal//4 molal MgCl2 solutions. Likewise, open circuit voltage decreased from 1.70 to 0.72 V. Evidence of uphill transport in the range of 0–30% MgCl2 was confirmed by Ion Chromatography analysis carried out on inlet and outlet streams of SGP-RE stack. Electrochemical Impedance Spectroscopy analysis revealed that cation exchange membrane resistance was critically affected by Mg2+ concentration: membrane resistance, from a value of 2.41 Ω cm2 in pure NaCl solution, increased tenfold in pure MgCl2 solution.