The Nd isotopic compositions (εNd) of mixed planktonic foraminifera have been analyzed in two sediment cores collected in the Nile deep-sea fan in order to reconstruct past εNd of the Eastern Mediterranean Deep Water (EMDW) and to assess the relative contributions of Nile discharge and Modified Atlantic Water (MAW) inflow to the Eastern Mediterranean Sea hydrology, as well as their potential control on anoxic events over the last climatic cycle. The two foraminiferal εNd records are similar and display an increase in εNd values during the African Humid Periods. Superimposed on this precession-forced variability (insolation received by the Earth at low latitudes), the record of variations in foraminiferal εNd indicates a 2-unit decrease in εNd during the interglacial Marine Isotope Stages (MIS) 5 and 1 compared to glacial MIS6, 4, 3 and 2. The εNd results suggest that the long-term glacial to interglacial changes in Nd isotopic composition of EMDW were not entirely induced by variations in Nile River discharge and Saharan dust inputs. Decreases in εNd during MIS5 and MIS1 interglacials indicate an increase in the contribution of unradiogenic MAW to the eastern Mediterranean Sea related to high sea-level stands and greater seawater exchange between the North Atlantic and Mediterranean basins. In addition, radiogenic seawater εNd values observed during African Humid Periods (and sapropel events) are associated with an intensification of Nile discharge and an increase in residence time of deep-water masses in the eastern Mediterranean Sea, which induces an increase in the interaction between deep-water masses and radiogenic sediments along the margin of the eastern Mediterranean Sea. Results confirm that an intensification of the hydrological exchanges between the western and eastern Mediterranean basins during high sea-level stand and the subsequent higher proportion of Atlantic Water in the Levantine Basin may have preconditioned the eastern Mediterranean Sea to sapropel depositions during the last climatic cycle.