The National Survey of Adolescents in Middle and High Schools on Health and Substance Use (EnCLASS) is an anonymous survey based on a self-administered online questionnaire. The 2022 data collection took place in 147 middle schools and 90 high schools in mainland France, involving 11,886 students. The indicators analyzed in this publication pertain to perceptions and attitudes toward mental health, mental disorders, and the well-being of middle and/or high school students. The key findings are as follows: The majority of middle and high school students perceive themselves as being in good health and are satisfied with their current lives. 59% of middle school students and 51% of high school students report a good level of mental well-being; 21% of middle school students and 27% of high school students report feeling lonely; 51% of middle school students and 58% of high school students report recurring physical and/or psychological symptoms; 14% of middle school students and 15% of high school students are at high risk for depression; 24% of high school students report having had suicidal thoughts in the past 12 months, 13% report having attempted suicide at some point in their lives, and about 3% report a suicide attempt that resulted in hospitalization; Students’ mental health and well-being deteriorate during middle school and do not improve in high school; Overall, girls have poorer mental health and lower levels of well-being than boys; Over the 2018–2022 period, middle school and high school students experienced a decline in their mental health and well-being, which was more pronounced among girls.