Information about the taxonomy and ecology of polychaetes from Caribbean Mesophotic Coral Ecosystems (MCEs) is limited. To fill this information void, substrata samples were collected using technical diving from several mesophotic localities (between 40–91 m depth) in Puerto Rico and the U.S. Virgin Islands between 2007 and 2012. A total of 76 genera, distributed among 34 families, were identified. All genera have previously been reported from the Caribbean and from other marine ecoregions. Syllidae was the best-represented family across all sampled localities with the largest number of genera (15) and the highest number of individuals (5,755, or 80.85% of the total records). Haplosyllis was the most abundant and most frequently sampled genus in the sampled sites. Bajo de Sico, a mesophotic coral ecosystem (MCE) off the west coast of Puerto Rico, was the location with the highest abundances (1,183 worms), while the MCE of the extended insular shelf off La Parguera Natural Reserve on the southwest coast of Puerto Rico had the highest number of genera (59), perhaps related to higher sampling effort and its greater spatial heterogeneity. In our qualitative samples, the abundances and number of Polychaeta genera tended to be higher in the shallower sites (<60 m) than in the deeper ones (>60 m).