Many arid and semi-arid regions of the world face growing freshwater scarcity, requiring increased utilization of seawater desalination to augment the existing freshwater resources. Seawater reverse osmosis (RO) is currently one of the most deployed technologies, due to its electrical energy efficiency and comparatively low costs. However, the required energy for desalination processes is often still converted from fossil sources. Given the growing demand for seawater desalination and the energy sector’s parallel decarbonization, the substitution by renewable energy sources (RES) is a critical issue. The volatility, lower availability of renewable energy, and cost for required electrical energy storage (EES) are all obstacles to the decarbonization of large-scale desalination plants and may affect production volume and water production costs negatively.This paper presents a mathematical model to determine a cost-optimal energy conversion and EES mix for the design and operation of large-scale seawater RO desalination plants. The linear program ensures satisfaction of the plant’s energetic demands. Furthermore, the model allows to investigate the general feasibility of integrating RES into large-scale desalination processes, which are examined by means of a case study while employing location-specific weather data. Different types of energy conversion technologies and the effect of EES on operating behavior, greenhouse gas emissions, and water unit costs are investigated. Specifically, the indirect storage of electrical energy via the smart management of a desalination plant’s oversized RO membranes is examined and compared to battery energy storage (BES).Results indicate that RES cannot meet an RO desalination plant’s full and constant electrical load demand without a high BES capacity, which is probably not feasible from a technical and economic point of view. The economic penalty from energy storage costs on one unit of desalinated water ranges from 3.10 $/m3 up to 5.38 $/m3. However, operating an oversized RO desalination plant intermittently could reduce the energy-related costs substantially and potentially provide a more appropriate way of adapting to a volatile supply of energy from renewable sources in order to decarbonize the desalination processes. Specific emissions of desalinated water can be reduced from 1.5 kg CO2 eq./m3 when relying mostly on combined cycle gas turbines down to 0.124 kg CO2 eq./m3 by intermittent operation and fully relying on renewable energy sources.