BackgroundFatty acid ethanolamides (FAEs) possess roles in energy regulation, however, the nutritional efficacy of various blends of oils on 7 key FAE levels altogether and their effects on body weight have not been characterized.ObjectiveTo assess the response of circulating levels of 7 FAEs, as well as food intake, fat oxidation, and body composition, to diets differing in dietary fatty acid composition.MethodTo address these objectives an animal trial (n=115) using different dietary oils was carried out. Animals consumed for two months (i) corn+safflower (C+S), (ii) flaxseed oil+safflower oil (F+S), (iii) regular canola oil (RC), (iv) high oleic canola oil (HOCO), (v) high oleic canola oil+DHA (H+DHA), (vi) high oleic canola oil+EPA (H+EPA), or (vii) olive oil (OO). Respiratory gas exchange was assessed for each animal to determine percentage fat oxidation (%FO) and carbohydrate oxidation (%CO). Total dietary fatty acid profile was assessed using GC‐FID. Plasma FAE levels were analyzed by UPLC‐MS/MS.ResultsPlasma oleoylethanolamide (OEA) levels were found to be the highest (p<0.05) with the OO as well as HOCO treatments. Also, diminished (p<0.05) food intake was observed in groups fed OO and HOCO treatments. Highest (p<0.05) fat mass was observed in C+S treatment when compared with F+S and OO treatments. Elevated (p<0.05) %FO was observed in OO treatment followed by H+EPA, H+DHA, F+S, and HOCO feeding when compared with C+S. Overall, among all dietary treatments, eicosapentaenoylethanolamide (EPEA) levels associated with increased food intake (r = 0.31024, p<0.0010). Also, across all dietary treatments, arachidonoylethanolamide (AEA) showed negative correlations with EPEA and docosahexaenoylethanolamide (DHEA), r = −0.33394 (p<0.0004) and r = −0.33320 (p<0.0013), respectively.ConclusionReduced food intake with the HOCO treatment, together with increased OEA concentrations, suggest anorexic properties of monounsaturated fat containing oils. Data show that AEA is associated with EPEA and DHEA concentrations; these associations might affect the food intake thereby modulating appetite. Similar findings observed during the feeding of OO, HOCO, and HOCO with omega‐3 fatty acids blends confirm the efficacy of HOCO in providing satiety alike OO. Therefore, it is concluded that incorporation of HOCO into diets could be valuable for the maintenance of healthy body weight and improve overall wellness similar to OO.Support or Funding InformationNatural Sciences and Engineering Research Council of Canada (NSERC)