Rationale: The technique used to provide continuous positive airway pressure to the newborn may influence lung function and breathing efficiency. Objectives: To compare differences in gas exchange physiology and lung injury resulting from treatment of respiratory distress with either bubble or constant pressure continuous positive airway pressure and to determine if the applied flow influences short-term outcomes. Methods: Lambs (133 d gestation; term is 150 d) born via cesarean section were weighed, intubated and treated with continuous positive airway pressure for 3 h. Two groups were treated with 8 L/min applied flow using the bubble (n=12) or the constant pressure (n=12) technique. A third group (n=10) received the bubble method with 12 L/min bias flow. Measurements at study completion included arterial blood gases, oxygraphy, capnography, tidal flow, multiple breath washout, lung mechanics, static pressure-volume curves and bronchoalveolar lavage protein. Measurements and Main Results: Birth weight and arterial gas variables at 15 min were comparable. Flow (8 or 12 L/min) did not influence the 3 hour outcomes in the bubble group. Bubble technique was associated with a higher pH, PaO2, oxygen uptake, and area under the flow volume curve, and a decreased alveolar protein, respiratory quotient, PaCO2 and ventilation inhomogeneity compared to the constant pressure group. Conclusions: Compared to constant pressure technique, bubble continuous positive airway pressure promotes enhanced airway patency during treatment of acute postnatal respiratory disease in preterm lambs and may offer protection against lung injury.