Highlights: The majority of middle school students perceive themselves as being in good health (nearly 9 out of 10 students) and report a positive outlook on life (more than 8 out of 10 students). Despite being in good health and having a positive outlook on life, one-third of 8th and 9th graders exhibit moderate or high levels of depression, and 4 out of 10 students exhibit a syndrome of complaints (somatic and/or psychological). Girls perceive their physical and psychological health as poorer than boys do (lower perceived health, less positive outlook on life, higher prevalence of symptom syndrome, and higher levels of depression). Girls’ mental health shows a negative trend between 6th and 9th grade (decreases in perceived health and positive outlook on life), while boys’ mental health remains stable. Over the 2010–2014 period, the proportion of girls with a positive perception of their lives decreased, and symptom clusters increased for both genders.