Morjana Alaoui, the actress who plays Anna, broke three bones in her foot during the shoot when she fell 3 meters (9.8 ft) off a soundstage. She had to stay in bed for six weeks, and production was temporarily halted for over a month.
Mylène Jampanoï and Morjana Alaoui, the actresses who play Lucie and Anna, both accepted their parts after being impressed and affected by the screenplay; Jampanoï even took the role over her agent's reservations. In preparation for filming, the actresses did two months of rehearsals with director Pascal Laugier, and to keep them in a heightened emotional state during the shoot, Laugier kept them isolated from the rest of the crew. Both stated in an interview that they found the shoot so emotionally difficult that they would never work with the director again, with Jampanoï recalling: "Every night when I went back to my room, I just cried, because I was so physically and psychologically tired. All my scenes are violent." Though she respected Laugier's working style, she found him to be "as short-tempered as me... I have a huge amount of admiration for him... but we did end up clashing".
Director Pascal Laugier has confessed that he wrote the screenplay for the film in a state of clinical depression, bordering on suicidal thoughts, which is why the film is said to have a nihilistic and depressing subject matter. He added that he was inspired by seeing Eli Roth's Hostel (2005) to "make a movie about pain", but has strongly denounced his film's inclusion in the New French Extremity movement, a wave of French movies from the 1990s/2000s with explicit violent and sexual content.
Special makeup effects artist Benoît Lestang committed suicide a few months before the movie's French premiere.
The North-American distribution rights were obtained by The Weinstein Company, but studio owner Bob Weinstein was so horrified by the film that he skipped the theatrical release, and had the movie released directly on DVD through a partner company, in both an unrated edition and a heavily edited, R-rated version. The movie was later remade as Martyrs (2015) by producer Jason Blum's Blumhouse Productions, something that Blum regretted in hindsight. Pascal Laugier, director of the French original, called selling off the remake rights the only regret in his career, as he hated the American version, and the fact that he didn't get any money from it due to negotiating a bad contract.