Oxygenated unsaturated fatty acids, known as oxylipins, are signaling molecules commonly used for cell-to-cell communication in eukaryotes. However, a role for oxylipins in mediating communication in prokaryotes has not previously been described. Bacteria mainly communicate via quorum sensing, which involves the production and detection of diverse small molecules termed autoinducers. Here we show that oleic acid-derived oxylipins produced by Pseudomonas aeruginosa function as autoinducers of a novel quorum sensing system. We found that this system controls the cell density-dependent expression of a gene subset independently of the quorum sensing systems thus far described in this bacterium. We identified a LysR-type transcriptional regulator as the primary receptor of the oxylipin signal. The discovery of this oxylipin-dependent quorum sensing system reveals that prokaryote-derived oxylipins also mediate cell-to-cell communication in bacteria.