Beef cattle industry could benefit from the identification of individuals with superior feed efficiency. Thus, biomarkers should be developed and validated to contribute to this objective. This study aimed to explore plasma biomarkers of residual feed intake (RFI) in fattening beef cattle through a targeted metabolomics approach. For this, 167 young Charolais bulls were tested for RFI in 3 independent cohorts during at least 6 months. Animals within each cohort were evenly assigned to either a high-starch corn silage diet or a high-fibre grass silage diet. Blood was sampled from each animal one month before the end of the test. Plasma from the 48 most extreme animals in terms of RFI (24 low vs 24 high RFI; balanced within cohorts and diets) were analysed for 630 metabolites by FIA- or LC- tandem mass spectrometry. Metabolites were analysed by ANOVA separately for each diet including the fixed effect of cohort, RFI group and their interaction. In the corn silage diet, plasma concentration of the 3 branched-chain amino acids (BCAA; Leu, Ile and Val) was lower (-15%; P≤0.01) in low-compared to high-RFI, likely reflecting their higher metabolic use for protein synthesis and muscle accretion. In contrast, creatinine and hydroxyl-proline, markers of muscle and collagen body mass respectively, showed higher plasma concentration (+18-20%; P≤0.01) in low- compared to high-RFI animals. In the grass silage diet, most of the RFI discriminant metabolites belonged to different classes of triglycerides and their plasma concentrations were always higher (+50% on average; P=0.003) in low- compared to high RFI animals, indicating either their lower incorporation into fat cells or their lower use as energy substrate by the muscle. Only creatinine was a common RFI discriminant metabolite in the two diets and Val, though also discriminant, showed opposite trends. Our results suggest that discriminant metabolites of RFI are not the same across two contrasting diets. However, differences in muscle body mass revealed by plasma creatinine concentration seems to be a determinant of RFI regardless the diet.