The closure of schools, social hubs, and extracurricular activities due to lockdown measures imposed to curb the spread of SARS-CoV-2, has increased the risk factors for students' mental health. This cross-sectional study, conducted from March 2020 to March 2021, aimed to estimate socio-emotional, cognitive, and affective disorders and substance use in a sample of first- and second-grade high school students in Northern Italy. This study compared data from 284 Italian students' self-perceptions along with the perceptions of their parents and teachers through a web-based survey. The differences in the perceptions of the three groups (students, parents, and teachers) were analyzed using an analysis of variance test, applying a Bonferroni correction. The X[superscript 2] test was used to assess the comparison between students, parents, and teachers in the substance use questions. The results showed statistically significant differences among the three groups. The most important outcomes were sociality, scholastic performance, extracurricular activity, emotional symptoms, affective disorders (depression and anxiety), and substance use. These findings could be interesting for the promotion of mental health and prevention of psychopathological risks in students.