Background: The COVID-19 pandemic has led to rapid acceleration in the deployment of new digital technologies to improve both accessibility and quality of care, and to protect staff. Mixed reality technology is the latest iteration of telemedicine innovation and is logical next step in the move towards the provision of digitally supported clinical care and medical education. The technology has the potential to revolutionise care both during and after the COVID-19 pandemic. Objective: This pilot project sought to deploy the HoloLens2™ mixed reality (MR) device to support the delivery of remote care in COVID-19 hospital environments. Methods: A prospective observational nested cohort evaluation of the HoloLens2™ was undertaken across three distinct clinical clusters in a UK teaching hospital. Data pertaining to staff exposure to high-risk COVID-19 environments and PPE use were collected, and assessments of acceptability and feasibility conducted. Results: The deployment of HoloLens2™ led to a 51·5% reduction in time exposed to harm for staff looking after COVID-19 patients (3·32 vs. 1·63 hours/day/staff member, p=0·002), and a 83·1% reduction in the amount of PPE used (178 vs. 30 items/round/day, p=0·017). This represents 222.98hrs reduced staff exposure to COVID-19, and 3,100 fewer items of PPE used each week across the three clusters evaluated. The majority of staff using the device agreed it was easy to set up and comfortable to wear, improved the quality of care and decision making, and led to better teamwork and communication. 89·3% of users felt that their clinical team was safer when using the HoloLens2™. Conclusions: New technologies have a role in minimising exposure to nosocomial infection, optimising the use of PPE and enhancing aspects of care. Deploying such technologies at pace requires context specific information security, infection control, and user experience and workflow integration to be addressed at the outset and led by the clinical end-users. The deployment of new telemedicine technology must be supported with objective evidence for its safety and effectiveness to ensure maximum impact.