Introduction The objective of our present study is to evaluate the impact of different PEEP levels on cerebral hemodynamic, gas exchanges and respiratory system mechanics in paediatric patients with post-traumatic brain swelling treated with decompressive craniectomy (DC). Materials and methods A prospective physiologic study was carried out on 14 paediatric patients presenting with severe traumatic brain swelling treated with DC. Transcranial Doppler ultrasonography was performed on the middle cerebral artery bilaterally after DC. After assessment at ZEEP, intracranial pressure (ICP), cerebral perfusion pressure (CPP), mean arterial pressure (MAP), central venous pressure (CVP) and gas exchanges were recorded at PEEP 4 and PEEP 8. Results From ZEEP to PEEP 8, the compliance of respiratory system indexed to the weight of the patient significantly increased (P = 0.02) without ICP modifications. No significant variation of the MAP, CPP, Vmed, the total resistance of respiratory system and ohmic resistance of the respiratory system indexed to the weight of the patients was observed. CVP significantly increased between ZEEP and PEEP 8 (P = 0.005), and between PEEP 4 and PEEP 8 (P = 0.05). Conclusions PEEP values up to 8 cmH20 seem to be safe in paediatric patients with a severe post-traumatic brain swelling treated with DC.