Background: The world is affected by the spread of Covid-19 especially nurses. A good knowledge of the infection process and control would support the willingness and commitment of nurses to perform their duties. Aim: To determine the relationship between nurses' knowledge, practice and barriers they perceived during outbreak of COVID-19 and their intention to leave. Design: A cross-sectional descriptive design was used. Subjects: It is a purposive sample of 254 nurses who had at least 6 months of experience who work in Medical, Surgical, Obstetrics & Gynecological, Pediatric, Operations, Emergency and ICUs units at Qena University Hospitals. Tools: Four tools were used for data collection; nurses knowledge questionnaire, nurses practice questionnaire, nurses perceived barriers questionnaire and staff nurses' intention to leave scale. Results: The majority of nurses had good knowledge and satisfactory level of practice towards COVID-19. The mean score of nurses' intention to leave was 76.64 illustrated is it high intention to leave. There were highly positive statistically significant correlation between nurses' knowledge and their practice towards covid19, and between nurse's intention to leave and barriers as perceived by them. There were highly negative statistically significant correlation between nurses' practice and barriers. Conclusion: The majority of studied nurses had good level of knowledge about COVID-19 and they had satisfactory level of practice towards COVID-19, barriers as perceived by nurses during COVID-19 outbreak were highly effective in nurses' intention to leave. Recommendations: Nursing managers should be providing comprehensive training program for nurses during and after the outbreak to ensure their knowledge and practice.