A solar thermal and photovoltaic-powered reverse osmosis (RO) desalination plant has been constructed and optimized for brackish water desalination. The central composite experimental design of orthogonal type and response surface methodology (RSM) have been used to develop predictive models for simulation and optimization of different responses such as the salt rejection coefficient, the specific permeate flux and the RO specific performance index that takes into consideration the salt rejection coefficient, the permeate flux, the energy consumption and the conversion factor. The considered input variables were the feed temperature, the feed flow-rate and the feed pressure. Analysis of variance (ANOVA) has been employed to test the significance of the RSM polynomial models. The optimum operating conditions have been determined using the step adjusting gradient method. An optimum RO specific performance index has been achieved experimentally under the obtained optimal conditions. The RO optimized plant guarantees a potable water production of 0.2 m³/day with energy consumption lower than 1.3kWh/m³.