Stewart, whose last major role on the big screen was that of Timlin in David Cronenberg's Crimes of the Future, will play a gym employee, while O'Brian is the person pumping iron.
Speaking of Crimes, Stewart previously addressed the body horror's many Cannes Film Festival walkouts last year.
"Everyone loves to talk about how his (Cronenberg's) movies are difficult to watch and it's fun to talk about people walking out of Cannes screenings," Stewart told Insider after the premiere.
"Every single gaping, weird bruise in his movies, it makes my mouth open. You wanna lean in toward it. And it never repulses me ever. The way I feel, it is through really visceral desire and that's the only reason we're alive. We're pleasure sacks."
Meanwhile, filmmaker Glass exclusively told Digital Spy all about her decision to show the eponymous Saint Maud protagonist (played by Morfydd Clark) burning herself to death in the movie's final, unforgettable shot.
"I always wanted the film to work on both levels, and you could interpret your way throughout [but] at what point does faith become a delusion? I know, for me personally, I have respect throughout the film that she's got her truth and the way that she's seeing things," she explained.
"Maybe some of that is kind of a genuine relationship with God, which maybe then descends into something more unhealthy, or maybe it was psychosis in the beginning.
"[However] as far as I'm concerned, by that point at the end of the film, she's obviously got to such a dangerous point where, regardless of what you think is going on, she's not capable to take care of herself, and she's in a really dangerous situation."
Love Lies Bleeding doesn't yet have a release date.
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