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Pregnant women are among the high-risk populations for COVID-19, whereas the risk of vertical transmission to the fetus is very low. Nevertheless, metabolic alternations described in COVID-19 patients may also occur in pregnant women and their offspring. We prospectively evaluated the plasma lipidomic and metabolomic profiles, soon after birth, in neonates born to infected mothers (cases, <i>n </i>= 10) and in the offspring of uninfected ones at delivery (controls, <i>n </i>= 10). All cases had two negative tests for SARS-CoV-2 (nasopharyngeal swabs) performed 72 h apart. Blood samples were obtained within the first hours after birth. Liquid chromatography-high resolution mass spectrometry (UHPLC-TOF/MS) and gas chromatography-mass spectrometry (GC-MS) were applied for the analyses. Multivariate statistical analysis was performed for data evaluation. Changes in several plasma lipid species-classes (long-chain fatty acids phosphatidylcholines, triglycerides), and amino-acids were identified that allowed for clear discrimination between the study groups. The results of this preliminary investigation suggest that neonates born to Sars-Cov-19 positive mothers, without evidence of viral infection at birth, have a distinct plasma lipidomic and metabolomic profile compared to those of uninfected mothers. Whether these findings are reflective of maternal metabolic alternations due to the virus or a metabolic response following an unidentified neonatal infection warrants further investigation.