OBJECTIVE: No single diagnostic investigation is currently available for necrotising enterocolitis (NEC). We implemented a novel, untargeted, exploratory study to determine whether metabolomics can reveal early biomarker(s) of NEC. The effect of gestational age on the metabolome was also investigated. METHODS: Two serum samples were obtained from 12 preterm babies (born <30 weeks gestation) and eight term controls: sample "A" at ≤1 week of age and sample "B" once fully fed. Samples were subjected to gas chromatography-mass spectrometry. Metabolomic data was analysed by principal component analysis (PCA), univariate and network analysis. RESULTS: Sixteen metabolite features significantly differed when B samples were compared between preterm babies who subsequently developed NEC and preterm/term controls (p value <0.05). Of these seven metabolites were linked to up-regulation of IL-1β. Significant differences in 54 metabolite features (p value <0.05) were observed between preterm and term metabolomes. Of these, 12 metabolite features were linked to one network involved in carbohydrate/lipid metabolism (p = 1 × 10(-30)). CONCLUSIONS: Metabolomic differences were observed in preterm babies at risk of NEC. However, sample sizes were insufficient to confidently identify a biomarker. Network modelling of preterm and term metabolomes suggest possible nutritional deficiency and altered pro-insulin action in preterm babies.