Slow-growing piglets during the post-weaning period continue to lag behind their fast-growing counterparts through to the finishing period, leading to a weight variability at slaughter that reduces farm profitability. Fast-growing piglets are associated with higher feed intake (1), yet nutritional strategies to increase nutrient intake in slow-growers around weaning have had limited success. In addition, light-weight piglets may not respond to increased nutrient supply (2), suggesting that growth variability may reflect intrinsic metabolic differences in nutrient processing and utilisation. The metabolic phenotypes emerging during the early post-weaning transition among healthy piglets with divergent growth trajectories remain poorly characterised. This study aimed to identify baseline differences in nutrient metabolic pathways between slow- versus fast-growing piglets in the post-weaning phase. We hypothesised that plasma metabolic profiles would reveal alterations in carbohydrate, fatty acid, and amino acid metabolism in slow-growers. Two extreme growth phenotypes were characterised from 23 piglets weaned at 21 days of age into fast (9.57 ± 1.45 kg, n = 12) and slow (5.06 ± 1.49 kg, n = 11) groups, initially blocked by weaning weight and monitored for 14 days after weaning. Untargeted metabolomic profiling of blood plasma collected at weaning was performed using liquid chromatography–time-of-flight mass spectrometry (LC-TOF-MS) in sequential window acquisition of all theoretical ion spectra (SWATH) mode. Chromatography data were analysed in MetaboAnalyst 6.0. Differential metabolites were identified by volcano plot analysis (fold change > 1 and p < 0.05) and annotated using MS-FINDER (v3.61). The abundance of 395 metabolites differed significantly between the two groups, with 214 upregulated and 181 downregulated in slow- compared to fast-growing piglets. These metabolites were mapped to 24 enriched KEGG pathways, including biosynthesis of unsaturated fatty acids, arachidonic acid metabolism, phenylalanine/tyrosine/tryptophan metabolism, and ascorbate and aldarate metabolism. Slow-growing piglets exhibited marked downregulation of several long-chain and polyunsaturated fatty acids (PUFAs), notably arachidonic acid (AA), docosahexaenoic acid (DHA), γ-linolenic acid, palmitic acid, and docosadienoate (22:2n6). Consistent with the reduced arachidonic acid profile, slow-growers also had lower levels of eicosanoid derivatives such as leukotriene C4. Sow milk contains adequate essential fatty acids, thus, the observed PUFA deficits in slow-growers may reflect intrinsic inefficiencies in uptake or reduced milk intake (3). Limited literature on baseline PUFA deficiency in suckling or newly weaned piglets underscores the novelty of these findings and highlights a potentially underexplored mechanism in early-life growth restriction. Human and rodent models link low DHA and AA to systemic inflammation in neonates and growth-restricted phenotypes (4, 5). These results identify early-life metabolic signatures that may underpin growth divergence and highlight lipid metabolism as a potential target for nutritional intervention.