Healthcare workers (HCWs) are on the front line of defense against the coronavirus disease 2019 (COVID-19) pandemic. Inadequate knowledge and negative attitudes among HCWs can directly affect practices, leading to delayed diagnosis, poor infection control practices, and the spread of disease. Knowledge, attitude, and practice (KAP) is necessary for better management of COVID-19. Aim: This study aimed to evaluate the effect of evidence-based guidelines on nurses' performance regarding pandemic COVID -19 in Isolation Units. Design: A quasi experimental design was used. Setting: This study was conducted in Isolation Units at internal medicine Hospital with Agar, Internal Medicine Hospital, and Cardiothoracic Hospital attached to Zagazig University Hospitals in Sharkia Governorate, Egypt. Sample: A purposive sample of 50 nurses. Tools:1) Self-Administered questionnaire for nurses to assess nurses' demographic characteristics, and nurses' knowledge regarding COVID-19 disease (Pre/ Posttest), 2) Nurses' practices regarding COVID-19 (Pre/Posttest), and 3) Nurses' attitude Likert Scale towards COVID-19 (Pre/Posttest). Results: Most (96.0%) of the studied nurses had adequate self-reported practices towards preventive measures against COVID-19 after the intervention, compared to less than two-thirds (60.0%) had reported total inadequate practices in the pretest itself. There was a highly statistically significant positive correlation between nurses' total knowledge, practices and their attitudes towards COVID-19 before and after the intervention (P<0.01). Conclusion: the implementation of evidence-based guidelines regarding COVID-19 had a statistically significant effect in improving knowledge, practices and attitudes of nurses. Additionally, there was a highly statistically significant positive correlation between nurses' knowledge, practices, and their attitudes towards COVID-19 before and after the intervention, supporting the proposed hypotheses. Recommendations: The illustrated developed booklet should be accessible to all nurses caring for people with COVID-19 to use as a reference guide in their practice. Key Words: Evidence Based Guidelines, Nurses' Performance, and Pandemic COVID -19.