Abstract We present the first full water column Nd isotope (εNd) and concentration data for Caribbean seawater, as well as for stations close to the Orinoco River mouth and in the Florida Straits. The surface inflow into the southeastern Caribbean via the Guyana Current is characterized by an εNd signature of −10.9, which is a consequence of the mixing of relatively unradiogenic εNd signatures (−13.6) supplied by the Orinoco River with contributions from the Amazon River (∼−10). Despite the proximity to land, sub-surface and intermediate waters within the Caribbean largely retain the εNd signatures of their source water masses in the Atlantic. In contrast, the deep waters of the Caribbean show εNd signatures at least 3 εNd units more radiogenic than the inflowing Upper North Atlantic Deep Water (UNADW). A εNd shift from −13 to −9.7 can be explained by addition of radiogenic Nd to the deep Caribbean through weathering inputs from land. However, in order to balance such large shifts in εNd with at the same time modest increases in Nd concentrations, Nd must also be removed from seawater within the basin. It is suggested that the long residence time of deep waters in the Caribbean allows significant interaction of seawater with sinking particles and seafloor sediments resulting in more radiogenic values. These findings have implications for the use of εNd as a proxy for paleocirculation in restricted basins, in which the residence times of the deep waters are long.