Argentine midfielder Ledesma has not played for over a month as he struggles with an ankle injury.
The 24-year-old is now unlikely to be involved again this term, with Mowbray saying: "Manu's had a few aborted attempts at returning from the injury - the kid's desperate to play.
"It's ultimately been too sore when he's got his boots on and gone out on the training ground. He's had to come off and it looks like we're not going to see Manu again this season."
Friend tore his hamstring earlier this month and is also unlikely to feature.
"He's got a grade two hamstring and that's usually a minimum of four weeks. I think it's unlikely we'll see him again this season."