<b><i>Background:</i></b> Nasal continuous positive airway pressure (nCPAP) stabilizes the residual volume and may decrease the risk of ‘atelectotrauma', potentially promoting lung development in neonates. <b><i>Objectives:</i></b> To assess whether replacing nCPAP by low-flow O₂ by nasal cannula affects lung function expressed as the arterial/alveolar oxygen tension ratio (a/A pO₂ ratio) on postnatal day 28. <b><i>Methods:</i></b> Preterm infants (birth weight <1,500 g and gestational age, GA >26 + 0 weeks) stable on nCPAP between postnatal days 4 and 7 were randomized to nCPAP or low-flow O₂ by nasal cannula (<0.2 liters/min). Study criteria defined how to wean/restart respiratory support or change from low-flow O₂ to nCPAP and vice versa. Transcutaneous monitoring was used for the assessment of the a/A pO₂ ratio on day 28 using a head box for all infants for accurate measurement and to eliminate possible effects from nCPAP or low-flow O₂ on oxygen requirement. <b><i>Results:</i></b> We enrolled 52 infants (nCPAP group n = 30 and low-flow O₂ group n = 22). The a/A pO₂ ratio at 28 days was 0.43 ± 0.17 (nCPAP group) versus 0.48 ± 0.18 (p = 0.36). The duration of nCPAP was 16.4 (low-flow group) versus 41.1 days (nCPAP group), p < 0.001. There was no difference between groups in the fraction needing any respiratory support at 36 weeks' corrected age, length of stay, weight at discharge, and relative weight gain. <b><i>Conclusions:</i></b> Replacing nCPAP by low-flow O₂ in preterm infants with GA >26 weeks at the end of the first week of life did not seem to affect the a/A pO₂ ratio or weight gain negatively. Thus, prolonged nCPAP seems not to have a positive effect on lung function at 28 days of life and replacement by low-flow O₂ could reduce the cost of equipment and increase the ease of nursing.