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Background: Ruminants play a great role in sustainable livestock since they transform pastures, silage, and crop residues into high-quality human food (i.e. milk and beef). Animals with better ability to convert food into animal protein, measured as a trait called feed efficiency (FE), also produce less manure and greenhouse gas per kilogram of produced meat. Thus, the identification of high feed efficiency cattle is important for sustainable nutritional management. Our aim was to evaluate the potential of serum metabolites to identify FE of beef cattle before they enter the feedlot., Results: A total of 3598 and 4210 m/z features was detected in negative and positive ionization modes via liquid chromatography-mass spectrometry. A single feature was different between high and low FE groups. Network analysis (WGCNA) yielded the detection of 19 and 20 network modules of highly correlated features in negative and positive mode respectively, and 1 module of each acquisition mode was associated with RFI (r = 0.55, P < 0.05). Pathway enrichment analysis (Mummichog) yielded the Retinol metabolism pathway associated with feed efficiency in beef cattle in our conditions., Conclusion: Altogether, these findings demonstrate the existence of a serum-based metabolomic signature associated with feed efficiency in beef cattle before they enter the feedlot. We are now working to validate the use of metabolites for identification of feed efficient animals for sustainable nutritional management.