Coronavirus disease 2019 (COVID-19) may pose unique challenges to clinicians attempting to diagnose brain death in patients infected with the SARS-CoV-2. Among these challenges is the risk of aerosol generation during the traditional apnea testing using the insufflation technique in addition to the risk of complications due to SARS-CoV-2-related lung disease. In this article, we discuss these challenges and provide further guidance to minimize such risks to ensure safety of healthcare professionals and other patients. We also emphasize the importance of maintaining the standards of brain death determination in this critical time.