Currently, the main public health concern worldwide is the COVID-19 pandemic, caused by SARS-CoV-2, which was recently discovered and described. Due to its high pathogenicity and infectiousness, it is necessary to determine the risk healthcare professionals face every day while dealing with infected patients and contaminated biological samples. The purpose of this study was to assess Portuguese Biomedical Scientists’ risk of COVID-19 exposure and related stress appraisals. One hundred and forty participants completed online versions of the WHO’s Risk Assessment and Management of Exposure Survey and the Stress Appraisal Measure. Participants worked mainly in outpatient settings (45%), and in emergency services (28%). Twenty three percent of participants were exposed to COVID-19 through community exposure, and 39% through occupational exposure. Although 95% reported using personal protective equipment (PPE), 83.6% were at high risk of infection. However, the use of some types of PPE was related to the risk of exposure. Participants reported moderate perceptions of stress and threat, but also moderate perceptions of control over the situation. These results may contribute to a more efficient risk management of these professionals and prevent disease transmission in hospitals and communities.