Abstract: Background: The massive online courses (MOCs) can be a promising tool in enhancing nurses' knowledge and practices regarding infection prevention and control measures. E-learning provides a flexible and accessible platform for healthcare professionals to learn about infection prevention and control measures conveniently. Aim of this study was to evaluate the effect of massive online courses on improving nurses' performance regarding infection prevention measures. Research design: quasi experimental research design was used to conduct this study. Setting: The present study was conducted at Zagazig university Hospitals in Sharkia governorate, Egypt. Subjects: The study sample included a purposive sample of 128 nurses working in Zagazig university Hospitals. Tools of data collection: Two tools were used for collecting data; Self-reporting questionnaire for nurses to evaluate nurses' knowledge regarding Infection prevention measures and Observational checklist to evaluate nurses' practices regarding Infection prevention measures. Results: the study results showed that satisfactory total knowledge level in the pre phase was less than fifth of studied nurses (15.6 %) while in the post phase was less than two thirds of studied nurses (62.5%) had satisfactory knowledge. Regarding to satisfactory total practice level in the pre phase was 18% while in the post phase was 69.5%. Conclusion: MOCs have a significant impact on the knowledge and practices of healthcare professionals in infection prevention and control practices. The study's findings highlight the effectiveness of using MOCs in enhancing healthcare workers' knowledge and practice levels regarding infection prevention and control measures in healthcare settings.  MOCs provide a unique opportunity for healthcare professionals to learn through interactive means and to access the latest information on infection prevention and control practices.  Recommendations: Online learning can be an effective way to enhance knowledge and practices related to infection control and prevention. Further research is essential to establish the efficacy of MOCs in healthcare settings comprehensively.