Increasing rule compliance in adolescents is one of the greatest challenges during the pandemic. Understanding how different variables are related to compliance with COVID-19 regulations in adolescents is needed to improve policy and practice against it. This study aims to analyze how sociodemographic and educational variables such as sex, age, socioeconomic status, being in a minority group, academic performance and failure, and problem behavior at school are related to the compliance with some COVID-19 regulations in a representative sample of 1,498 students (aged between 11 and 17 years M = 13.58, SD = 1.32) of compulsory secondary education in Andalusia (Spain). Results showed that almost one out of three participants never kept the recommended social distancing. In contrast, nearly 85% of the participants wore a mask every day when they spent time with their peers. A higher number of failed subjects and school suspensions were related to less compliance, younger adolescents complied more with the COVID-19 measures and ethnic minorities were less compliant than the majorities. Regression analysis showed that the higher school performance, male sex, young age, being part of a sexual minority and feeling bad about the pandemic were uniquely related to more compliance with preventive measures. Programs to promote equalitarian education and programs to promote school success could be useful to increase the compliance in adolescents.