Human milk is recommended for feeding preterm infant. Yet the potential impact of specific breast-milk lipid components on the initial growth rate of very-preterm infants has received scant attention. The current pilot study aims to determine whether breast-milk lipidome had any impact on the early growth pattern of preterm infants fed their own mother’s milk. A prospective monocentric observational birth cohort was established, enrolling 147 preterm infants, who received their own mother’s breast-milk throughout hospital stay. Among that cohort, infants who experienced slow (n=15) or fast (n=11) growth were selected, based on the change in their weight Z-score between birth and hospital discharge (-1.54± 0.42 and -0.48± 0.19 Z-score, respectively). Liquid chromatography-high resolution-mass spectrometry was used to obtain lipidomic signatures in breast-milk. Multivariate analyses made it possible to identify breast-milk lipid species that allowed clear-cut discrimination between the 2 infants’ groups. Validation of the selected biomarkers was performed by means of various multidimensional statistical techniques, false-discovery rate and ROC curve computation. Breast-milk associated with fast growth contained more medium chain-saturated fatty acid and -sphingomyelin, dihomo-γ-linolenic acid (DGLA)-containing phosphethanolamine, and less oleic acid-containing triglyceride and DGLA-oxylipin. Their predictive ability of preterm early-growth rate was validated in presence of confounding clinical factors.