Background: Nurses' compliance with infection control practices is the key to quality and excellence in Covid-19 patient care; infection control remains one of the most cost beneficial and requires full compliance of the whole nursing team. Aim of the current study was to assess nursing staff compliance regarding infection control measures with COVID-19 patients at isolation hospitals. Design: Descriptive cross sectional study design was utilized to fulfill the aim of this study.   Setting The study was conducted in two of corona virus's isolation hospitals at Minia City, Minia governorate, Egypt (Minia Chest Hospital & Minia Fever Hospital). Subjects: The study sample included (233) of nursing staff working in the prementioned hospitals, who were on duty during the period of data collection. Data Collection Tool: Observational Checklist of Nursing Staff Compliance with Infection Control and Prevention consisting of two parts; personal data sheet followed by Observation Checklist items. Results: Most of the studied nursing staff at the two hospitals had high level of compliance with infection control measures, while (12.4%) of them had low compliance level. Also, most of the studied nursing staff at Minia fever hospital had high compliance with protective measures, and linen management, while most of the studied nursing staff at Minia chest hospital had high compliance with safe injection practices, and specimen handling with statistically significance. Conclusion: The mean scores of total compliance level as well as the mean scores of personal protective equipment and safe injection practices sub-domain were observed higher in the morning shift than in the other work shifts with high statistically significant differences. Recommendations: Continuous education and training for all health care sectors about all waves of the Covid -19 virus. Frequently supervision by management levels to ensure nursing staff compliance with infection control measures during all work shifts.