<p>Objective: The precision of oxygen saturation (SpO<sub>2</sub>) targeting in preterm infants on continuous positive airway pressure (CPAP) is incompletely characterized. We therefore evaluated SpO2 targeting in infants solely receiving CPAP, aiming to describe their SpO<sub>2</sub> profile, to document the frequency of prolonged hyperoxia and hypoxia episodes and of fraction of inspired oxygen (FiO<sub>2</sub>) adjustments, and to explore the relationships with neonatal intensive care unit operational factors.</p> <p>Study design: Preterm infants <37 weeks' gestation in 2 neonatal intensive care units were studied if they were receiving CPAP and in supplemental oxygen at the beginning of each 24-hour recording. SpO<sub>2</sub>, heart rate, and FiO<sub>2</sub> were recorded (sampling interval 1-2 seconds). We measured the proportion of time spent in predefined SpO<sub>2</sub> ranges, the frequency of prolonged episodes (≥30 seconds) of SpO<sub>2</sub> deviation, and the effect of operational factors including nurse-patient ratio.</p> <p>Results: A total of 4034 usable hours of data were recorded from 45 infants of gestation 30 (27-32) weeks (median [IQR]). When requiring supplemental oxygen, infants were in the target SpO<sub>2</sub> range (88%-92%) for only 31% (19%-39%) of total recording time, with 48 (6.9-90) episodes per 24 hours of severe hyperoxia (SpO<sub>2</sub> ≥98%), and 9.0 (1.6-21) episodes per 24 hours of hypoxia (SpO<sub>2</sub> <80%). An increased frequency of prolonged hyperoxia in supplemental oxygen was noted when nurses were each caring for more patients. Adjustments to FiO<sub>2</sub> were made 25 (16-41) times per day.</p> <p>Conclusion: SpO<sub>2</sub> targeting is challenging in preterm infants receiving CPAP support, with a high proportion of time spent outside the target range and frequent prolonged hypoxic and hyperoxic episodes.</p>