Background: During COVID-19 global health care crisis, the systems of health care around the world as well as the financial, emotional, and physical well-being of their health care workers (HCWs) are at risk due to the overwhelming burden caused by the illness and its mortality nature. Nurses play a crucial role in fighting pandemics, also they are at greater risk of COVID-19 infection due to their duties full of stressors that may endanger their health, that require effective coping strategies. Objective of the study: This research paper aims to assess the stress, the coping responses of nurses, and the relationship between them throughout the COVID-19 outbreak in isolation and quarantine hospitals at El Beheira Governorate. Methods and materials: Design: In this study, a descriptive correlational design was used. Setting: The study was performed in the isolation and quarantine hospitals at El Beheira Governorate. Sampling: A random sample of 300 nurses participated in the study and selected through proportional allocation from the previously mentioned settings. Study Tools: This study employed two tools. namely, tool (I) is COVID-19 Nursing Stress questionnaire including the nurses' sociodemographic characteristics and a survey of nurses' stress level regarding COVID-19 pandemic, while tool (II) is way of coping questionnaire.Results It was noticed that less than one fifth (17.7%) of the nurses had high stress, and less than one quarter (23.7%) had low stress. It was found that over 25% (28.7%) of the nurses used emotion-focused coping strategies at a high level, while over one third (34.0%) of the nurses used cognitive-focused coping strategies at a high-level Conclusion: From the previous results it was concluded that stress is a prevailing problem among nurses that require continuous workshops and training courses to help them dealing with their perceived stress.