The charity's annual report revealed that nearly 250,000 youngsters say they are unhappy and that kids overall wellbeing is at its lowest level since 2009.
Spokesperson Matt Hussey told Premier the Children's Society is "deeply concerned" by the results of the 2019 survey.
He said the findings reveal a growing level of anxiety among today's youth: "Children are particularly worried about the future - about things like Brexit and climate change all the way to more personal issues, such as not having enough money in the future and not being able to find a job.
"It's really worrying that children feel weighed down by these big issues of the day."
The study found that factors like friendship, school and body image were also contributing factors to their self-esteem, with nearly one in 12 boys aged 10 to 15 saying they didn't like their appearance.
"Boys are feeling increasingly under pressure, to go to the gym, to look a certain way, to follow fashion. So what we're seeing is an unfortunate downward trend in the way that boys are feeling about the way they look."
Body confidence is still a bigger issue among young women, but the gap between boys and girls on this topic is narrowing, according to the report.
Hussey says children are feeling more isolated and alone in their problems: "Substantial numbers of children feel like they have nobody they can turn to and nobody they can talk to. A really good way of building friendships, is spending time with other young people outside of school, but we're seeing that children are doing a bit less of that in recent years."
Hussey says the Church is well placed to help young people struggling with loneliness and self-esteem issues: "It's really important that the Church and others are challenging gender stereotypes to make sure that children feel confident about themselves and confident in their own bodies."
"Youth groups are a great way to bring young people together to promote positive relationships and friendships, but also to give them a safe space to talk about issues that are concerning them."
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