Introduction: In the early phase after severe brain injury, patients are often bedridden in an attempt to control intracranial homeostasis; however, prolonged immobilisation may trigger complications. There is limited knowledge about the physiological effects of mobilisation in this early phase. Objective: To investigate changes in brain tissue oxygen tension when patients are mobilised using a Sara Combilizer® in the early phase after severe brain injury, in a randomised cross-over design. Methods: Patients with traumatic brain injury, subarachnoid haemorrhage or intracranial haematoma, will be randomised to early mobilisation or rest (no mobilisation = control) on the first day that the patient is deemed to be fit for mobilisation, and the opposite on the next day. On both days, patients will undergo continuous multimodal monitoring measuring brain tissue oxygen tension (primary outcome), invasive blood pressure, heart rate, middle cerebral artery blood flow velocity by transcranial Doppler ultrasound, intracranial pressure, and microdialysis markers of cerebral oxidative metabolism. Discussion: Intensive care unit patients with acute brain injury are frequently immobilised in the early phase after the ictus. The optimal timing and intensity of mobilisation is unknown. The present study attempts to establish if early mobilisation is safe with respect to intracranial homeostasis. Protocol version 1.1. Date: 19.02.2022. Ethical registration: H-21002728; approved on August 11, 2021. GDPR registration: P-2021 − 105; approved on February 10, 2021. ClinicalTrials.govidentifier:NCT05038930; approved on September 8, 2021. Electronic case report file: REDCap-database; created on August 13, 2021.