<b><i>Introduction:</i></b> Carbon dioxide (pCO₂) induces changes in the tone of cerebral vessels. The aim of the present study was to evaluate the impact of pCO₂ on cerebral regional tissue oxygen saturation (crSO₂), cerebral fractional tissue oxygen extraction (cFTOE), and cerebral tissue oxygen extraction (cTOE), measured with near-infrared spectroscopy (NIRS), in preterm and term infants 15 min after birth. <b><i>Methods:</i></b> Post hoc analyses of

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... y outcome parameters of prospective observational studies were performed. Stable preterm and term infants with cerebral NIRS monitoring (INVOS 5100C) until minute 15 after birth and a blood gas analysis, performed between minutes 14–18 after birth, were included. Heart rate (HR) and arterial oxygen saturation (SpO₂) were recorded. pCO₂ was correlated with crSO₂, cFTOE, cTOE, SpO₂, HR, and partial pressure of oxygen (pO₂). <b><i>Results:</i></b> Eleven preterm infants with a median (IQR) gestational age of 34.8 (32.7–36.1) weeks were analyzed. Mean ± SD pCO₂ was 53.5 ± 4.2 mm Hg. At minute 15 after birth, crSO₂ was 82.6 (74.3–91.3)%, cFTOE 0.15 ± 0.09, cTOE 14.6 ± 8.4%, SpO₂ 97.4 ± 2.1%, and HR 152 (136–167) bpm. pCO₂ correlated negatively with crSO₂ (<i>p</i> = 0.012) and positively with cFTOE (<i>p</i> = 0.035) and cTOE (<i>p</i> = 0.037). Eighty-four term infants with a gestational age of 39.0 (38.5–38.9) weeks were analyzed. pCO₂ was 53.5 ± 6.3 mm Hg. At minute 15 after birth, crSO₂ was 84.4 (80.8–85.1)%, cFTOE 0.14 ± 0.08, cTOE 13.6 ± 7.9%, SpO₂ 96.5 ± 2.6%, and HR 155 (153–163) bpm. pCO₂ did only negatively correlate with pO₂ (<i>p</i> = 0.034) in term infants. <b><i>Conclusion:</i></b> In preterm infants, higher pCO₂ was associated with lower crSO₂ and higher cFTOE/cTOE. In term infants, no associations were observed. The present findings suggest that the vasodilatative effect of pCO₂ is less pronounced in preterm infants during immediate postnatal transition.