Background: Egypt has the fastest-growing HIV epidemic in the Middle East and North Africa (MENA) region. Nursing students need adequate knowledge and a positive attitude toward HIV/AIDS for effective patient care. Objective(s): This study assessed nursing students' knowledge and attitudes toward HIV/AIDS. Methods: A cross-sectional study among 400 randomly selected nursing students at Damanhur University used a self-administered questionnaire. Knowledge and attitude scores were analyzed using SPSS. Results: Knowledge and attitude scores were significantly better among females (p=0.023, p=0.038, respectively). Areas of knowledge deficiency included misconceptions about HIV transmission through mosquito bites and sharing personal items. Additionally, only 19.0% correctly identified that no recent vaccine exists. Negative attitudes were prevalent, with 53.3% believing AIDS hinders education and employment, and 61.5% were uncomfortable working with HIV-positive colleagues. Academic year influenced both knowledge and attitudes, with second-year students scoring highest (p < 0.001, p=0.004). A weak but significant correlation was found between knowledge and attitude scores (r=0.138, p=0.006). Conclusion: Misconceptions and negative attitudes toward HIV/AIDS persist among nursing students, highlighting the need for targeted educational interventions. Gender and academic year significantly influenced knowledge and attitudes, emphasizing the role of curriculum development in addressing gaps. Strengthening HIV/AIDS education and stigma-reduction initiatives is crucial to preparing future nurses for competent and compassionate care.