The purpose of this article is to analyze the severity of stress reactions and identify the predictors of psychological maladaptation of medical workers in the context of the COVID-19 pandemic, as well as to compare the prevalence of psychological well-being disorders in doctors and medical staff during the current COVID-19 pandemic and previous outbreaks of 21st-century infectious diseases. The article shows that the COVID-19 pandemic has become a challenge for health care systems in all countries. On the base of the analysis of international studies of the emotional status of medical workers during pandemic COVID-19 and previous outbreaks of infectious diseases, in this article, there are discussed the factors of physical and psychological distress of medical staff in the pandemic COVID-19. There are considered the prevalence of negative psychological reactions and mental states in doctors and medical staff during the pandemic, such as acute stress reactions, anxiety disorders, depressive experiences, and sleep disorders. There are highlighted the predictors of the occurrence of negative emotional experiences in medical workers in the context of the COVID-19 pandemic and in the future. In the article, there is discussed the specifics of working in the “red zone” and its impact on the emotional well-being of medical workers, especially on the emotional state of nurses as the most vulnerable group. The formation of attachment between medical professionals and patients with COVID-19 in the “red zone” is discussed. On the base of the analysis of previous outbreaks of infectious diseases, there are estimated the probability of developing such adverse conditions and disorders as burnout syndrome, post-traumatic stress disorder (PTSD), alcoholism, and substance abuse in health care workers in the long term. The concern is expressed about the high incidence of burnout among doctors and medical staff in the context of pandemic that may affect the quality of medical care in the absence of timely psychological assistance.