The endogenous lipid messenger OEA inhibits eating and modulates fat metabolism supposedly through the activation of PPAR-α and vagal sensory fibers. We tested in adult male rats whether OEA stimulates fatty acid oxidation (FAO) and ketogenesis and whether it increases plasma levels of the satiating gut peptides glucagon-like peptide-1 (GLP-1) and peptide tyrosine-tyrosine (PYY). We also explored whether OEA still inhibits eating after subdiaphragmatic vagal deafferentation (SDA). We found that intraperitoneally (IP) injected OEA (10 mg/kg body weight = BW) reduced (P < 0.05) food intake mainly by increasing meal latency and that this effect was stronger in rats fed a 60% high-fat diet (HFD) than in chow-fed rats. OEA increased (P < 0.05) postprandial plasma non-esterified fatty acids and β-hydroxybutyrate (BHB) in the hepatic portal vein (HPV) and vena cava (VC) 30 min after injection, which was more pronounced in HFD- than in chow-fed rats. OEA also increased the protein expression of the key-ketogenetic enzyme, mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase, in the jejunum of HFD-fed rats, but not in the liver or duodenum of either diet group. Furthermore, OEA decreased GLP-1 and PYY concentrations (Ps < 0.05) in the HPV and VC 30 min after administration. Finally, OEA reduced food intake in SDA and sham-operated rats similarly. Our findings indicate that neither intact abdominal vagal afferents nor prandial increases in GLP-1 or PYY are necessary for the satiety effect of OEA. The enhanced FAO and ketogenesis raise the possibility of an involvement of intestinal-derived BHB in OEA's satiety effect under certain conditions.