Coastal lagoons are particularly vulnerable to climate change, in particular, Sea Level Rise(SLR) due to their shallowness. Lake Burullus provides a variety of socio-economic services as the second largest coastal lagoon in Egypt. Recently, it has experienced significant ecological deterioration. Thus, its ecosystem is fragile in the face of anthropogenic induced changes. The main objective of the current study is to investigate the climate change impacts on characteristics of Lake Burullus. A depth averaged hydro-ecological modeling system, MIKE21, was applied to develop an eco-hydrodynamic model for the lake. The developed model was calibrated and verified for two successive years: July 2011 - June 2012 and July 2012 -J une 2013. The model simulations exhibited good agreement with the measurements during the calibration and verification processes. Six different Regional Climate Models(RCMs) were compared,using six different statistical metrics, to determine the most accurate one for the study area. The required meteorological input, including surface air temperature, precipitation, and evaporation were derived from the selected RCM. The meteorological input was extracted for two different years in the 21century considering one Representative Concentration Pathways(RCPs) scenario, based on the Intergovernmental Panel on Climate Change(IPCC) 5 th Report. Regional SLR projections for the Mediterranean Sea for the selected RCP scenario and the two studied years were obtained. These future climate change estimates were used to modify the validated model of the lake. A sensitivity analysis was applied to assess effect of future climatic conditions and SLR, separately. The results revealed that the lake water depths will increase and it will be warmer and more saline. Significant spatial variability of the studied parameters under climate change forcing is expected. Consequently, climate change is going to restrict the lake’s ability to preserve the present-day species. An urgent management plan involving adaptation works, should be implemented to reduce such potential species losses in Egyptian lagoons.