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Background: The COVID-19 pandemic has been linked to various psychological disorders, including anxiety, particularly among the general public. It is crucial to monitor the mental health of school students, who are considered a vulnerable group in society, and assess their self-efficacy, as it can significantly affect their mental health. This study aimed to investigate the levels of anxiety and self-efficacy among school students during the COVID-19 pandemic. Methods: This cross-sectional study utilized convenience sampling to examine a sample of 335 school students from Sistan and Baluchestan province in southeastern Iran. An online questionnaire, distributed through social media platforms, was used to collect data. The questionnaire included demographic information, COVID-19 related items, the Multidimensional Anxiety Scale for Children-MASC, and the Self-Efficacy Questionnaire for Children-SEQ-C. Data analysis was conducted using IBM SPSS version 24, with a significance level set at < 0.05. Results: The study revealed a significant negative correlation between children's anxiety and self-efficacy (r = -0.23, P < 0.001). Several factors were identified as predictors of anxiety, including low self-efficacy (β = -0.29, P < 0.001), female gender (β = 0.27, P < 0.001), concern about family members contracting COVID-19 (β = 0.18, P < 0.001), persistent advice of others to adopt preventive measures (β = 0.14, P < 0.005), level of education (β = -0.12, P < 0.017), and perceived risk of COVID-19 infection (β = -0.11, P < 0.030). These variables collectively accounted for 17% of the variance in anxiety. Conclusion: The findings of the study highlight the importance of addressing the mental health of school students, specifically their anxiety levels, during epidemics. The results also indicate that enhancing self-efficacy among students during a pandemic could be a beneficial strategy for promoting their mental health. [ABSTRACT FROM AUTHOR]