The Magdalena River mouth in Colombia is studied as a candidate site for a renewable power plant via osmotic energy technology, using pressure retarded osmosis. This power generation plant would operate through the controlled mix of two flows with different salinities (river water and seawater in this case study). A preliminary design of a pressure retarded osmosis power plant is proposed here by means of experimental data acquisition on-site at the river mouth. The obtained net power production is shown to reach 6 MW, with adequate membrane power densities above 5 W/m2. These promising results consider energetic losses involved in the process, which have been further analysed to propose improvement targets in pretreatment processes and membrane permeability.