<strong>Aims:</strong> This study quantifies to what extent Health care workers (HCWs) experienced moral stress and to what extent their experiences of moral stress were related to gender and age as well as to working directly with COVID-19 patients and other work-related factors. <strong>Methods:</strong> This study consists of a cross-sectional survey that was conducted among 16,044 Swedish HCWs. A total of 153,300 HCWs and support staff who participated in the COVID-19 training offered by the Karolinska Institute were invited by email to participate in a web survey during autumn 2020. <strong>Results:</strong> This study is the first to quantify the frequency and severity of moral stress in a large group of HCWs. Moral stress was reported to a higher extent by HCWs involved in COVID-19 care and those involved in direct patient care. A lack of resources and the restrictions that hindered the patients’ family and friends from being involved were major causes of moral stress. Informal support was reported as being the most available and useful for dealing with moral stress. <strong>Conclusions:</strong> Our findings suggest that moral stress is common among HCWs who work with infected patients during a pandemic. The goal should not be to eliminate moral stress, as such stress may be viewed as a normal reaction to moral issues, but organizational structures (sufficient staffing and resources), could decrease the likelihood of morally stressful situations. Finally, to avoid the development of moral distress and its potential consequences, improvements could be made in providing HCWs with support tools for managing moral stress.