Argentinian Ledesma is struggling to shake off a persistent ankle problem and has been restricted to a series of appearances as substitute.
Mowbray told the Evening Gazette: "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 are not going to see Manu again this season."
The news of Friend, who tore a hamstring during the 0-0 draw with Peterborough on April 2, is equally gloomy.
Mowbray added: "He's got a grade two hamstring, and that's usually a minimum of four weeks. I think it's unlikely we will see him again this season."