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Predator–prey interactions are a key feature of ecosystems and often chemically mediated, whereby individuals detect molecules in their environment that inform whether they should attack or defend. These molecules are largely unidentified, and their discovery is important for determining their ecological role in complex trophic systems. Homarine and trigonelline are two previously identified blue crab (Callinectes sapidus) urinary metabolites that cause mud crabs (Panopeus herbstii) to seek refuge, but it was unknown whether these molecules influence other species within this oyster reef system. In the current study, homarine, trigonelline, and blue crab urine were tested on juvenile oysters (Crassostrea virginica) to ascertain if the same molecules known to alter mud crab behavior also affect juvenile oyster morphology, thus mediating interactions between a generalist predator, a mesopredator, and a basal prey species. Oyster juveniles strengthened their shells in response to blue crab urine and when exposed to homarine and trigonelline in combination, especially at higher concentrations. This study builds upon previous work to pinpoint specific molecules from a generalist predator’s urine that induce defensive responses in two marine prey from different taxa and trophic levels, supporting the hypothesis that common fear molecules exist in ecological systems.