Objective: This study aimed to assess the knowledge and preventive behavior towards COVID-19 among secondary school students and teachers after re-opening of schools and associated factors, and to compare the two groups. Methods: This cross-sectional study was carried out in Saudi Arabia from the 1st of March 2022 to the 1st of April 2022. A self-administered questionnaire was distributed among school teachers and students to measure their knowledge about COVID-19 infection. Results: Out of 1228 participants, 404 were teachers and 821 were school students. The overall mean knowledge score was significantly higher in teachers (mean score: 9.30) than in school students (mean score: 8.95) (p