Description: Highlights: • The impact of brine discharge on coastal food-web was modeled. • Stable isotope data validated the simulated trophic structure. • Simulated and observed spatial-temporal biomass trends were comparable. • Simulated outflow brine plumes had limited impact on the food-web. • Temperature had a greater negative impact on biomass than salinity. Abstract: Population growth and climate change have led to an increasing demand for freshwater, and subsequently to an exponential growth of the seawater desalination industry in which the number of reverse osmosis-based plants is constantly increasing. The purpose of this study was to examine the possible impact of brine discharge on the marine food-web by constructing and analyzing food-web models from two desalination plant environments located along the Israeli coastline. The models were constructed using the Ecopath and Ecosim with Ecospace modeling suite, and analyses of collected samples were used for calibration and validation. Additionally, we conducted a series of scenarios in order to evaluate the impact of increased salinity and temperature on the food-web. A comparison between model output and measured isotopic δ15N values yielded a good fit. In addition, Ecopath results illustrated the importance of the zooplankton groups both in terms of biomass and trophic level. Ecospace results indicated that most functional groups biomass decreased compared to the "no desalination" scenario. The results indicate that elevated temperature most likely has a greater effect than increased salinity on the food-web, and that there is a general decrease in functional groups biomass due to desalination.