Sheffield United full-back Andy Taylor is likely to miss most of 2011, while Richard Cresswell is out for up to six weeks.
Taylor suffered a serious knee injury during the Boxing Day encounter against Hull City and he is facing months on the sidelines.
The defender has picked up a similar injury to team-mate Chris Morgan and he has been left devastated after scans confirmed the extent of the damage.
"It is the same injury that 'Morgs' suffered," Taylor told the club's official website. "I have damaged the lateral ligament and ACL in my left knee.
"It has been hard to take because you never think it is going to happen to you and I will be honest, it brought a tear to my eye when the news was confirmed."
Meanwhile, striker Cresswell is likely to be out until the middle of February after hurting his shoulder in Monday's 2-2 draw with Doncaster Rovers.
New Blades boss Micky Adams said: "He has done his shoulder.
"He is an honest kid and we're going to miss 'Cressy' because in the two games he has played for me he has been outstanding."