The 28-year-old megastar and the 29-year-old singer-songwriter have joined forces on the new track, which Sam penned before his single 'This City' became a global smash hit.
A press release states that the moving song is about the "feeling of being alone and not wanting to let people down".
Demi commented: “This song is a reflection on what it’s like to lose who you truly are in an effort to please other people and society. It’s why I wanted to make this song with Sam – ultimately it’s about two humans coming together to connect and find solutions to their problems.”
Sam said: "'What Other People Say' is a confession, realising how far away you can get from who you are in an effort to be liked. It’s about the pressures of society and how getting caught up with the wrong things can change you.”
The pair's duet news comes as Sam was crowned YouTube's first-ever Artist on the Rise for 2021.
Previous recipients include Mabel, Aitch, Freya Ridings, Mahalia, Beabadoobee and Celeste.
Meanwhile, Demi revealed in January that she felt compelled to hit the studio to channel her "anger" after Donald Trump supporters rioted in Washington D.C.
The 'Sorry Not Sorry' singer admitted she felt "embarrassed and ashamed" after the attack on the Capitol building by protestors calling for the presidential election results to be overturned and called for the impeachment of Trump.
Demi also slammed fans asking her where her seventh studio album is in such a pivotal moment in American history, but teased "something special" is on the way following the "assault on democracy".
In a series of tweets, she wrote: "My heart is broken. It makes me to sad to believe how naive I was to think this couldn’t possibly happen, and yet it did. Here we are. For everyone in my comments saying “where’s d7” or wanting me to sing instead of speaking up about what needs to change in this country...
THIS IS WHY I POST AS MUCH AS I DO. THIS IS WHY I CARE. THIS CANNOT HAPPEN ANY F****** MORE. I’m angry, embarrassed and ashamed.
I’m in the studio working on something special after today’s assault on democracy.
Last year, Demi released the political track, 'Commander in Chief', which features everything she would love to say to Trump if she had the chance.
She said: "There's been so many times that I've wanted to write the President a letter or sit down with him and ask him these questions.
"And then I thought, I don't really actually want to do that and I thought one way that I could do that is writing a song and releasing it for the whole world to hear and then he has to answer those questions to everyone and not just me.”