Allelopathy has been recently suggested as a mechanism by which macroalgae may outcompete corals in damaged reefs. Members of the brown algal genus Lobophora are commonly observed in close contact with scleractinian corals and have been considered responsible for negative effects of macroalgae to scleractinian corals. Recent field assays have suggested the potential role of chemical mediators in this interaction. We performed in situ bioassays testing the allelopathy of crude extracts and isolated compounds of several Lobophora species, naturally associated or not with corals, against four corals in New Caledonia. Our results showed that, regardless of their natural association with corals, organic extracts from species of the genus Lobophora are intrinsically capable of bleaching some coral species upon direct contact. Additionally, three new C21 polyunsaturated alcohols named lobophorenols A–C (1–3) were isolated and identified. Significant allelopathic effects against Acropora muricata were identified for these compounds. In situ observations in New Caledonia, however, indicated that while allelopathic interactions are likely to occur at the macroalgal-coral interface, Lobophora spp. rarely bleached their coral hosts. These findings are important toward our understanding of the importance of allelopathy versus other processes such as herbivory in the interaction between macroalgae and corals in reef ecosystems.