Abstract. Background: Exogenous surfactant is a mainstay of neonatal care, however, time-dependent changes in respiratory function during the peri-surfactant period are not well known. This critical time contributes to baro- and volu-trauma effects, heralding chronic lung disease. The purpose of the study was to determine real-time changes in respiratory function minuteby-minute during the immediate post-surfactant period and determine the effect of increased positive end-expiratory pressure (PEEP) on these parameters. Methods: Thirty, time-pregnant, Sprague-Dawley rat pups received surfactant or phosphate buffered saline (PBS) control between post-natal age 10 and 12 days. Airway resistance, compliance, tissue dampening, elastance, and eta (ratio of dampening to elastance), were measured at PEEPs of 3 and 6 cm H2O at 1, 2, 5, 8, 12 and 15-minutes. Pressure-volume curves were generated. Student’s t-test of running averages of each respiratory function parameter were used for comparison. Results: At PEEP of 6 cm H2O, airway resistance remained elevated at 12 minutes (p < 0.01), but was signiﬁcantly lower by 8 minutes in the group at PEEP of 3 cm H2O (p < 0.05). Increased PEEP led to earlier changes in tissue dampening (2 min vs. 8 min, p < 0.01), earlier increases in elastance (5 min vs. 8 min, p < 0.05), and an earlier alteration in eta (2 min vs. 15 min, p < 0.01). Time dependent pressure-volume loops demonstrated signiﬁcant decreases in variability within 2 minutes at PEEP of 3 (p < 0.001). The PV curves were normalized at 5 minutes. Conclusions: Acute minute-by-minute changes occur in airway resistance, elastance, compliance, eta, and tissue dampening following surfactant delivery, but normalize by 15 minutes. At higher PEEPs, respiratory parameters normalized earlier and variability in PV curves was reduced. Consideration of the time-dependent nature of respiratory function changes in the perisurfactant period may improve administration.