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Chemical defense against herbivores has rarely been investigated for freshwater plants, possibly due to the common misconception that herbivory on aquatic macrophytes is low and would not select for chemical defenses. In previous work, the freshwater angiosperm Saururus cernuus was shown to be a low preference food for omnivorous crayfish despite its high nutrient value and relatively soft texture. We used feeding by the crayfish Procambarus clarkii to guide fractionation of the deterrent lipid-soluble extract of this plant, leading to the identification of seven deterrent lignoid metabolites, (− )-licarin A, (+ )-saucernetin, (−)-dihydroguaiaretic acid, (− )-sauriols A and B, ( − )-saucerneol, and (− )-saucerneol methyl ether. Lignans have been implicated in terrestrial plant chemical defenses as insect growth inhibitors, insect toxins, nematocides, antibacterial, and antifungal agents. However, these activities have rarely been demonstrated using ecologically relevant methodologies in terrestrial systems, and never before in freshwater systems. The widespread nature of lignans amongst very distantly related plants, along with their rich diversity of molecular structure, suggests that they could play a large role in mediating plant-herbivore interactions. In addition to the lignoid compounds we identified, there were other compounds present in low concentration or unstable compounds that were deterrent, that did not appear to be lignans, but that we were unable to identify. This plant thus appears to be defended by a complex mixture of natural products.