This document aims to provide guidance to healthcare facilities and healthcare providers in the European Union/European Economic Area (EU/EEA) and the United Kingdom (UK) on preparedness and infection prevention and control (IPC) measures for the management of possible and confirmed cases of COVID-19 in healthcare settings, including long-term care facilities (LTCFs). In addition, this document addresses the management of clinical diagnostic specimens at laboratories in the EU/EEA. This is the sixth update of the ECDC guidance on ‘Infection prevention and control and preparedness for COVID-19 in healthcare settings’, and replaces the document dated 6 October 2020.