Introduction: Cord blood gas analysis reflects placental respiratory and metabolic function and is commonly used to assess fetal status at birth. Our aim was to identify the differences in blood gas parameters between the umbilical artery (UA) and umbilical vein (UV) in term and preterm infants. Methods: This was a prospective pilot study. Umbilical cord artery and UV samples were consecutively collected from 225 term and 57 preterm infants at the University Hospital of Padua and at the neonatal unit of Ruesch Hospital in Naples, Italy. Blood gas-analysis and glucose measurement were performed in all samples. Term infants were divided into adequate for gestational age (AGA) and small for gestational age (SGA) according to birth weight percentile. Data were analyzed using Pearson Product-Moment Correlation, independent-samples t-test, and paired-samples t-test. A p-value <0.05 was considered statistically significant. Results: The median gestational age of preterm and term newborns were 34 weeks (±2) and 39 weeks (±1) respectively. The pH, pO2, were lower and pCO2, HCO3 − and base excess (BE) were higher in the UA compared with the UV, in both AGA and SGA term infants. In preterm infants, no statistically significant differences were found between the UA and UV regarding pH, while the pO2 was lower and pCO2 was higher in the UA than UV (respectively: 22.5 vs. 32.4 and 53.1 vs. 42.8; p<0.0001). In the UA, pO2, BE and potassium (K +) were lower (respectively: 22.5 vs. 25.1;-2.5 vs.-3.7; 4.8 vs. 5.8; p<0.001) while sodium (Na +) and calcium (Ca ++) were higher in preterm than term newborns (respectively: 135.7 vs. 133.6; p<0.001; 1.4 vs. 1.3; p<0.001). Glycaemia was lower in the UA than in the UV in all newborns (respectively: 66 vs. 77 in AGA term newborns; 63 vs. 71 in SGA term newborns; 68 vs. 76 in preterm newborns; p<0.0001) and was related to venous glycaemia measured in the first hour of life (n= 282, r =0.60; p<0.001). Conclusions: Significant differences in blood gas parameters between the UA and UV in term and preterm newborns suggest the importance of the placental barrier and the need for accurate cord blood gas analysis interpretation at birth. UA and UV samples at birth are required to assess with higher accuracy the metabolic status of the newborn in utero. Further studies are needed to evaluate if cord glycemic values could be a noninvasive tool for prediction of glycaemia during the first hour of life.