"Never Let Me Go" is Carey Mulligan's favorite novel. She was certain someone would make a film adaptation, and had hoped they could wait until she was old enough to play Kathy. She couldn't bear the idea of anyone else portraying Kathy, although she acknowledged that she thought other people would be able to do a better performance. She actively campaigned for the role.
Carey Mulligan had to learn how to drive for the film. She took a two-week intensive course, but failed the driving test. Her scene was shot on a private road, where she was allowed to get behind the wheel.
Mark Romanek said that working with child actors was the most challenging part of making the film, since "the first act of the film was going to have to be carried by 12-year-olds." During pre-production, Romanek had the younger actors watch the older actors rehearse the younger scenes, so the older actors would have a memory of having played those scenes, while the child actors would get a better idea of how more skilled actors would play their parts. He also had the child actors spend time together, playing and talking to create chemistry between them. He took them to the school set and let them play there so they could get a better idea of the layout.
Keira Knightley admitted that she only agreed to appear in the film because her friend and co-star Carey Mulligan had asked her to. She said she was unable to relate to Ruth's involvement in a love triangle.