Background: There are few data available on the interaction of inflations, chest compressions (CC), and delivery of tidal volumes in newborn infants undergoing resuscitation in the presence of endotracheal tube (ET) leaks. Objectives: To determine the effects of different respiratory support strategies along with CC on changes in tidal volume and ET leaks in hypoxic newborn piglets with cardiac arrest. Methods: Asphyxiated newborn piglets, intubated with weight-adapted uncuffed ET, were randomized into three groups and resuscitated according to ILCOR 2010 guidelines: (1) T-piece resuscitator (TPR) group = peak inspiratory pressure (PIP)/positive end-expiratory pressure (PEEP) 25/5 cm H2O, rate 30/min, inflations interposed between CC (3:1 ratio); (2) self- inflating bag (SIB) group = PIP 25 cm H2O without PEEP, rate 30/min, inflations interposed between CC (3:1 ratio), and (3) ventilator group = PIP/PEEP of 25/5 cm H2O, rate 30/min. CC were applied with a rate of 120/min without synchrony to inflations. Results: We observed a significant increase of leak (average increase 11.4%) when CC was added to respiratory support (p = 0.0001). Expired tidal volume was larger in the SIB group than in the two other modes which both applied PEEP. However, tidal volumes caused by CC only were larger in the two groups with PEEP than in the SIB group (without PEEP). Conclusions: There is interaction between lung inflations and CC affecting leak and delivery of tidal volume, which may be influenced by the mode/device used for respiratory support. Leak is larger in the presence of PEEP. However, CC cause additional tidal volume which is larger in the presence of PEEP.