A new Scyllaeidae of the genus Notobryon is described from Guadeloupe, in the Lesser Antilles. Notobryon caribbaeus sp. nov. is characterized by having the anterior pair of body lobes remarkably bigger than the posterior pair, a stomach with eight triangular plates, a black and very wide ampulla, a lemon-shaped bursa copulatrix and a complex and well-differentiated sponge-like prostate. The first Caribbean records of Notobryon were provisionally assigned to the Australian species Notobryon cf. wardi and later transferred to Notobryon panamica. However, the structure of the male genital system is one of the main morphological characters to discriminate species in the genus and the presence of a prostate in N. caribbaeus sp. nov. distinguishes it from N. panamica, which remains confined to the eastern Pacific. Of the remaining four species in the world, only Notobryon bijecurum shares this character, but its external anatomy is different: it lacks a bursa copulatrix and the deferent duct is much shorter. Notobryon caribbaeus sp. nov. was captured in the context of an intensive expedition (‘Karubenthos’) organized by the Muséum National d'Histoire Naturelle, Paris and its description raises the total inventory of sea slugs in Guadeloupe to 150.