Meningitis is a serious health problem that is considered an endemic disease in Egypt. Nursing personnel play an active role in the control and management of meningitis Aim: to evaluate the effect of an educational instruction program on nurses' knowledge and practices regarding care of patients with meningitis. Design: A quasi experimental research design (pre- and post-test) was utilized. Setting: Helwan Fever Hospital in Helwan city, Egypt. Subjects: A convenient sample of all nurses working in selected settings (50 nurse). Tools for data collection: Three tools were used, including the nurses' personal characteristics, the knowledge assessment interview questionnaire, and the lumber puncture observational checklist. Results: the studied nurses gained a satisfactory level of knowledge (92%) during the post-test phase followed by follow-up test phase (90%) as compared with pre-test phase (34%). Moreover, there was a highly statistically significant difference between total mean score of knowledge as well as total mean score of practices throughout study phases among the studied nurses at P = 0.000. Significant positive correlation between of total knowledge and practices among the studied nurses. Conclusion: there was a highly statistically significant difference between total mean score of knowledge as well as practices during pre, post & three months follow up among studied nurses. Additionally, there was a large effect size of educational instruction program on nurses' knowledge and practices pre, post and follow-up educational instruction program. Recommendations: Periodical on-the-job training programs for nurses regarding the management of meningitis.