Background: Anemia constitutes a problem of serious public health significance, given its impact on psychological and physical development, behavior and work performance. Objectives: The aim of the present study was to estimate the prevalence of anemia, its extent and determinants among secondary school students in El-Kharga, and to identify the effects of anemia on students' performance. Methods: The study was conducted using a cross-sectional approach. It included 330 secondary school students allocated to different schools according to the number of secondary school students attending each school. A predesigned structured interviewing questionnaire was used to collect data from the students. Anthropometric measurements (weight and height), body mass index and laboratory investigations were done. School records were reviewed for the grades of the previous exams. Results: The prevalence of anemia among secondary school adolescents in El-Kharga was 51.8%. Infection with parasites, total energy calories, plant protein, total carbohydrate and iron from plant origin were significantly higher among anemic school students than among normal students. The logistic regression model showed that only those who were infected with parasites had a higher significant risk of anemia and plant protein had a protective effect compared to relevant categories. Anemic students had more than four and half times less scholastic achievements than the normal students. Conclusion: The prevalence of anemia among school adolescents in El-Kharga indicates a public health problem based on the WHO epidemiological criteria for diagnosis of anemia.