Background: COVID-19 is an ongoing pandemic, for which appropriate infection prevention and control measures need to be adopted. Healthcare workers' adherence to prevention and control measures is affected by their knowledge, attitudes, and their psychological responses towards COVID-19. Aim of the study: is to assess nursing staff knowledge, attitude, and psychological response of COVID-19 during COVID-19 outbreak. Research design: a descriptive correlational research design. Setting: conducted at the Minia Health Insurance Hospital. Subjects: all nursing staff at the time of data collection (no=280). Data collection: data was collected by using four tools. Results: the study showed that majority (97.1%) of nursing staff had satisfied total knowledge about COVID-19; the majority (87.5%) of nursing staff had a favorable attitude toward COVID-19; more than half that (53.6%) of nursing staff had a moderate level of fear from COVID-19 and finally, more than half (51.8%) of nursing staff had a moderate level of total anxiety from COVID-19. Conclusion: it was observed that there is a weak positive association between total nursing staff knowledge about COVID-19 and their total attitude toward COVID-19. While, there is a weak negative association between nursing staff knowledge about COVID-19 and their total fear score; and there is a negative but not significant association between knowledge about COVID-19 and their total anxiety score. Recommendation: All nurses should have access to personal protective equipment at all times, especially those working in isolation hospitals, and there should be training sessions provided on COVID-19 protection.