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Background: Adolescent high school students may be particularly susceptible to suffering from the effect of isolation, physical distancing restrictions, and school closures imposed during the COVID-19 (Corona Virus Disease 2019) pandemic. Given the biological and psychological changes that occur during this period of development, adolescents' experiences of these pandemic measures could significantly threaten their mental health and cause long-term consequences., Aim: The main objectives of the study were to determine the impact of confinement because of the COVID-19 pandemic restrictions on the psychological distress of Moroccan adolescents and identify the risk and protective factors that could influence their mental health., Methods: The participants in this study were Moroccan high school students who were recruited at two different times-before the COVID-19 pandemic (350 students, mean age: 16.55 years; 53.71% female; data collected in 2014/2015) and after the announcement of the pandemic (457 students, mean age: 16.84; 64.1% female; data collected in 2020). Students responded to an anonymous survey that included several validated instruments, such as the Brief Symptom Inventory and the Godin-Shephard Leisure-Time Physical Activity questionary, and elicited information about the students' psychosocial environment, gender, and age. The scores on the Brief Symptom Inventory dimensions from the pre-pandemic period and during 2020 were compared. A comparison between the scores of the two genders of the 2020 sample was also carried out. In addition, binary regression analysis was performed to predict the associations between gender, frequency of physical activity, the presence of the number of negative psychosocial factors, and those dimensions of the Brief Symptom Inventory that significantly changed between the samples., Results: Female students reported higher psychological distress than male students in both data collection periods. During the COVID-19 pandemic, students scored significantly ( p < 0.001) higher in depression and paranoid ideation, and they scored significantly ( p = 0.01) lower in hostility and anxiety compared with the pre-pandemic period. Female gender and the experience of physical or psychological abuse significantly increased the risk of reporting higher scores in depression and paranoid ideation symptoms during 2020. Moderate and frequent physical activities were significantly and negatively associated with depression ( p = 0.003 and p = 0.004; respectively)., Conclusions: This study confirms the stressful impact of the COVID-19 pandemic on Moroccan high school students, who reported more symptoms of depression and paranoid ideation compared with the pre-COVID-19 period. Female students reported higher psychological distress than male students did. The experience of physical /psychological abuse during the pandemic worsened mental health, while moderate/frequent physical activity improved it., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Mzadi, Zouini, Kerekes and Senhaji.)