Presented at the 2015 Aquarius/SAC-D Science Team MeetingLarge rivers are key elements of the global hydrologic cycle and important links between terrestrial hydrology with the ocean. The freshwater associated with major river plumes can influence air-sea interaction by affecting the vertical stratification in the surface layer and thus the efficiency of vertical heat transfer. The Mississippi River, the largest river in North America, provides a major contribution of freshwater into the Gulf of Mexico and has implications to ocean circulation in the subtropical North Atlantic. Monitoring of the spatial and temporal variability of the Mississippi plume extension is therefore important to the physics and biophysical interaction at regional and basin scales. In this study, we use data from the NASA Aquarius/SAC-D and ESA SMOS satellites to study the seasonal and interannual variations of sea surface salinity (SSS) in the Gulf of Mexico near the outflow of the Mississippi River. A seasonal cycle is clearly observed in the SSS, with SSS maximum occurring in December-April and SSS minimum in July. The magnitude of the seasonal change is about 4 psu. Interannual changes are also observed over the 2010-2014 period, with the lowest SSS in summer 2011 (30 psu) and the highest SSS in summer 2012 (33 psu). Therefore, the interannual changes magnitude is comparable to that of the seasonal cycle. Our analysis suggests that the seasonal and interannual variations of SSS near the mouth of the Mississippi River are consistent with variations in the River discharge. Evaporation minus precipitation (E-P) flux plays a minor role.