The Channel of Sicily, which represents the only connection between the western and the eastern Mediterranean Sea, can be described as a three-layer system, where fresher water of Atlantic origin (Modified Atlantic Water) flows eastward in the upper layer, Levantine Intermediate Water (LIW) leaves the eastern basin at around 250–350 m, and an outflow of Transitional Ionian Deep Water (TIDW) is identified below the LIW. Synoptic Mesoscale Plankton Experiment data, collected during four surveys in the Channel of Sicily, show that LIW and TIDW are subject to major modifications when crossing the eastern sill. A significant Bernoulli aspiration is found there, and the bottom water at the sill is composed of modified deep Ionian waters coming from >800 m. An analysis of the water mass composition proves that LIW mixes essentially with TIDW, and that the TIDW flow through the channel must be larger than the expected 0.5 Sv. The presence of a secondary circulation related to the bottom boundary layer is demonstrated to be the primary factor leading to the dilution and cooling of LIW.