Perry has infamously battled substance addiction and depression.
An insider said, "Just because Jen isn't super close to Matthew doesn't mean she isn't scared for him. She's tried making contact numerous times over the past few years, but he rarely returns calls and when he does it's like talking to a different person."
All the former sitcom stars are "desperately sad to see Matt in such a bad way and his state of mind is a big reason why the Friends reunion hasn't gotten off the ground yet. But that's not their main concern – it's seeing him struggle so badly that's breaking their hearts."
As Radar reported earlier this year, Perry's February social media admission that he was kicked out of therapy set off alarm bells with his former Friends co-stars.
He soon returned to therapy.
Perry has been aloof with the other ex-Friends stars: "He's had his issues with some of them through the years, but that was due to the way he was behaving during those dark party days," a source said.
The sitcom cast members "are all united in their shared mission to get him back on track," revealed the source.
They vowed to all check up on him, according to the informant, and even loan him money if he needs it.
Perry previously revealed that he had surgery to repair a ruptured bowel and spent "three months in a hospital bed."
In June, Perry was seen out in public for the first time in almost two years following his recent health battles.
Photographers caught the funnyman looking disheveled and bloated in Manhattan.
He looked rough in loose-fitting stained clothes, and a large mark marred his right cheek.
Perry, who dated actress Lizzy Caplan from 2006 to 2012, is currently unattached.
He's never been married and doesn't have any children.
Meanwhile, Aniston, Cox and Kudrow recently shared a mini-Friends reunion for Cox's 55th birthday.
Aniston said to Ellen DeGeneres about a real Friends TV reunion, "Listen, I told you this, I would do it. The girls would do it. And the boys would do it, I'm sure."
Fans of the mega-hit NBC show rejoiced at the idea, but would Perry be able to participate?