With a severe seasonal concentration of precipitation and unevenly distributed water resources, the water supply in Portugal is under stress, and the problem is expected to increase with climate change. Water desalination is increasingly becoming the preferred solution to fight water scarcity, but, because it is energy-intensive, the underlying costs and sustainability concerns over the power sources chosen remain a challenge to its implementation. This study aims to assess if the introduction of renewable energy sources (RES) powered desalination in mainland Portugal is viable and can contribute to guarantee water security. The Portuguese Algarve region is a viable case study to be considered because it is particularly water stressed and subject to highly varying demographics depending on the season. Taking the region’s freshwater demand, hourly RES production and power demand, a cost analysis was performed in order to obtain the levelized cost of water (LCOW) for two different strategies (centralized and decentralized). Two models were developed to estimate the LCOW: a simplified model and a subsequent optimization model, minimizing electricity costs. The resulting LCOW of 72.66 c€/m³, obtained for the decentralized solution, fits within the industry standard rate despite being 61.3% higher than the estimated conventional water supply production cost.