Objective: There is an ongoing debate about the best and comfortable way to administer surfactant. We hypothesized that uninterrupted respiratory support and continuous PEEP implementation while instilling surfactant via endotracheal tube (ETT) with side port will result in higher regional cerebral tissue oxygenation (rcSO2) and the alterations in cerebral hemodynamics will be minimal. Methods: Preterm infants who required intubation in the delivery room and/or in the first 24 hours of life with gestational age <32 were enrolled. Patients were intubated either via conventional ETT or ETT with side port (Vygon®) with appropriate sizes. Following NICU admission a NIRS probe placed on the forehead and each infant were monitored with NIRS.In conventional ETT group, patients separated from the ventilator while surfactant was instilled. In ETT with side port group respiratory support was not interrupted during instillation. Heart rate, oxygen saturations, rcSO2, cerebral fractional tissue oxygen extraction (cFTOE) and blood pressures were recorded. Results: A total of 46 infants analyzed. Surfactant was instilled with conventional ETT in 23 and ETT with side port in 23 infants. Birthweights (1037±238 vs 1152±277g) and gestational ages (28±2.3 vs 29±1.6weeks) did not differ between groups. During instillation of surfactant, rcSO2 levels [61.5 (49-90) vs 70 (48-85)] and cFTOE levels 0.28 (0.10-0.44) vs 0.23 (0.03-0.44)] were similar (p=0.58 and 0.82 respectively). Conclusion: Interruption of respiratory support during surfactant instillation did not significantly alter the cerebral tissue oxygenation. These results did not support our hypothesis possibly due to small sample size and should be confirmed with further studies.