Diversity patterns of the deep-sea megafauna in the Caribbean Basin and the Guiana ecoregion were analyzed in order to test the hypothesis of species richness variation as a function of depth and the hypothesis of non-differences between ecoregions by analyzing spatial patterns of five taxa and a merged assemblage. Collections of five taxa (corals, sea stars, sea urchins, sea lilies and gastropods) were obtained from seven oceanographic expeditions aboard the R/V Pillsbury at 310 stations between 60 and 7500 m depth. Data were sorted according to depth zones and ecoregions and were analyzed in order to estimate species richness, changes in species composition and distinction of β-diversity by species turnover or by nestedness. The observed patterns of diversity were consistent between taxa and their assemblage: Species richness increased from the continental shelf (60-200 m deep) to the slope (200-2000 m deep), followed by a decrease at the continental rise-abyssal zone. We detected marked changes in species composition according to depth ranges. Changes in species composition in relation to ecoregions were also detected. In general, the Caribbean Basin lacks important physical barriers, causing high deep-sea ecosystem connectivity; however, variation in composition could be related to changes in environmental conditions associated with productivity and/or continental influences.