To provide information to guide considerations of declaring interruption of transmission of human schistosomiasis due to Schistosoma mansoni on St. Lucia, we undertook an island-wide survey in June-July 2022 to determine the presence of Biomphalaria snails, the intermediate hosts of S. mansoni, and their infection status. Snail surveys were carried out at 58 habitats to determine presence of Biomphalaria snails followed by examination of the collected snails for evidence of infection with S. mansoni. Furthermore, water samples were collected at the snail habitats and screened for presence of S. mansoni DNA using an eDNA approach. We found B. glabrata present in one habitat (Cul de Sac) where it was abundant. Specimens provisionally identified as Biomphalaria kuhniana were recovered from 10 habitats. None of the Biomphalaria specimens recovered were positive for S. mansoni. None of the eDNA water samples screened were positive for S. mansoni. Experimental exposures of both field-derived and laboratory-reared St. Lucian B. glabrata and B. kuhniana to Puerto Rican and Kenyan-derived S. mansoni strains revealed B. glabrata to be susceptible to both and B. kuhniana proved refractory from histological and snail shedding results. We conclude, given the current rarity of B. glabrata on the island and lack of evidence for the presence of S. mansoni, that transmission is unlikely to be ongoing. Coupled with negative results from recent human serological surveys, and implementation of improved sanitation and provision of safe water supplies, St. Lucia should be considered a candidate for declaration of interruption of human schistosomiasis transmission.