BACKGROUND Diagnosis of necrotizing enterocolitis (NEC) in preterm neonates is challenging. We hypothesized that regional splanchnic oxygen saturation (rsSO₂) measured by near-infrared spectroscopy (NIRS) is a biomarker for mesenteric perfusion. OBJECTIVE To evaluate feasibility and safety of continuous rsSO₂ monitoring in preterm infants in the first 14 days of life. METHODS Preterm neonates ≤30 weeks' gestation had a NIRS sensor placed in the left paraumbilical region within 48 h of birth. rsSO₂ was recorded every 30 s. Clinical data including pulse oximetry (SaO₂) were recorded. Fractional tissue oxygen extraction (FTOE) was computed as follows: (SaO₂ - rsSO₂) × 100/SaO₂. RESULTS Of 21 infants enrolled, 2 were excluded because of skin breakdown and missing data. Daily mean rsSO₂ values decreased over the first 9 days (p < 0.0001) followed by an increase from day 10 (D10) to D14 (p = 0.0061). rsSO(2) was lower and FTOE was higher in infants with feeding intolerance compared to those without feeding intolerance (p = 0.0043). rsSO₂ accounted for ≥99.5% of the variance in FTOE. Two neonates with NEC had persistently low rsSO₂ with loss of variability preceded or followed by very high rsSO₂. CONCLUSIONS We have reported feasibility, safety and ranges for rsSO₂ for a small number of preterm infants in the first 2 weeks of life.