Introduction: Supplemental oxygen therapy is a mainstay of modern neonatal intensive care for preterm infants. However, both insufficient and excess oxygen delivery are associated with adverse outcomes. Automated or closed loop FiO2 control has been developed to keep SpO2 within a predefined target range more effectively. Methods: The aim of this study was to investigate the feasibility of closed loop FiO2 control by Predictive Intelligent Control of Oxygenation (PRICO) on the Fabian ventilator in maintaining SpO2 within a target range (88/89-95%) in preterm infants on different modes of invasive and noninvasive respiratory support. In two tertiary neonatal intensive care units, preterm infants with an FiO2 >0.21 were included and received an 8 h nonblinded treatment period of closed loop FiO2 control by PRICO, flanked by two 8 h control periods of routine manual control (RMC1 and RMC2). Results: 32 preterm infants were included (median gestational age 26 + 5 weeks [IQR 25 + 5-27 + 6], median birthweight 828 grams [IQR 704-930]). Six patients received invasive respiratory support, while 26 received noninvasive respiratory support (18 CPAP, 4 DuoPAP, and 4 nasal IMV). The time percentage within the SpO2 target range was increased with PRICO (74.4% [IQR 67.8-78.5]) compared to RMC1 (65.8% [IQR 51.1-77.8]; p = 0.011) and RMC2 (60.6% [IQR 56.2-66.6]; p < 0.001) with an estimated median difference of 6.0% (95% CI 1.2-11.5) and 9.8% (95% CI 6.0-13.0), respectively. Conclusion: In preterm infants on invasive and noninvasive respiratory supports, closed loop FiO2 control by PRICO compared to RMC is feasible and superior in maintaining SpO2 within target ranges.