The Eastern Mediterranean Sea (EMS) is a key region to study circulation change because of its own thermohaline circulation. In this study, we focused on intermediate/deep water circulation since the Last Glacial Maximum (LGM) including the sapropel S1 period. Two cores from the Levantine Sea and the Strait of Sicily, respectively, collected at 1,780 m and 771 m water depth, were studied using Nd-143/Nd-144 (epsilon(Nd)) of foraminiferal tests and leachates as well as benthic foraminiferal stable isotopes (delta C-13, delta O-18). This approach allowed the determination of variations in (1) the North Atlantic water contribution to the Mediterranean basin, (2) water exchanges at the Strait of Sicily, and (3) the influence of the Nile River over the last 23,000 years. During the LGM, high benthic foraminiferal delta C-13 values indicate well-ventilated intermediate and deep waters in the EMS. The epsilon(Nd) values were more radiogenic than at present, reflecting a smaller contribution of unradiogenic North Atlantic waters to the EMS due to reduced exchange at the Strait of Sicily. The sluggish circulation in the EMS initiated during deglaciation was further enhanced by increased Nile River freshwater inputs between 15 ka BP and the S1 period. Partial dissolution of Nile River particles contributed to an increase in EMS epsilon(Nd). The large epsilon(Nd) gradient between the EMS and the Western Mediterranean Sea observed during LGM and S1 suggests that each basin had a distinct circulation mode. Decreasing epsilon(Nd) values at the Strait of Sicily after S1 reflected improved water exchange between both basins, leading to the modern circulation pattern.