Sea Surface Salinity (SSS) measurements from the Soil Moisture and Ocean Salinity (SMOS) mission provide an unprecedented opportunity to observe the salinity structure of tropical instability waves (TIWs) from space, especially during the intense 2010 La Niña condition. In the eastern equatorial Pacific Ocean, SMOS SSS signals correlate well and have similar amplitude to 1 m salinity from the Tropical Atmosphere Ocean (TAO) array at six locations with strong TIW signals. At these locations, the linear negative relationships between SMOS SSS and OSTIA SST signals vary from −0.20°C−1 to −0.25°C−1, which are comparable to the ones obtained from TAO. From June to December 2010, the largest TIW signals and meridional gradients of both SSS and SST appear around 2°N west of 100°W. They shift southward and cross the equator at 90°W. In addition to the large negative correlation band around 2°N, a band of negative correlations between SSS and SST signals also exists around 8°N west of 110°W for the 33 day signals. The peak amplitude of the 33 day SMOS SSS signals west of 135°W is reduced by >40% with respect to values east of 135°W, while the reduction for SST is much lower (<20%). The amplitudes and longitudinal extents of TIW signals and the dominant westward propagation speed of 17 day TIWs (as detected by SMOS and Aquarius) at the equator decrease from 2010 to 2013 associated with the transition from a strong La Niña to non-La Niña conditions.