The Argentine playmaker has been suffering from an ankle injury, which has prevented him from a regular staring role.
Meanwhile, young full-back Friend tore his hamstring during last weekend's goalless draw with Peterborough United.
"Manu's (Ledesman) had a few aborted attempts at returning from the injury - the kid's desperate to play," manager Tony Mowbray told the Evening Gazette.
"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.
"[George has] 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."
Boro are currently 10th in the Championship.