Scotland will be without key backs Tommy Seymour, Blair Kinghorn and Stuart Hogg for Saturday's Calcutta Cup clash with England at Twickenham.
Hogg has been out since the second round of Six Nations fixtures last month, injuring his shoulder in the defeat against Ireland.
He has been joined on the sidelines by Seymour, who suffered a rib injury against Wales on Saturday, and Kinghorn who sustained an ankle problem in the same game.
Neither will have sufficient time to recover for Scotland's final game in the 2019 tournament, according to the national team's medical staff.
Scotland's head coach Gregor Townsend has added Glasgow Warriors pair Ruaridh Jackson and uncapped Kyle Steyn to the squad.
Fellow Warriors Adam Ashe and Tim Swinson, plus Edinburgh pair James Johnstone and Luke Crosbie have been released back to their clubs.
Scotland have only won one of their four games in the Six Nations so far this season, their opener against Italy, but gave Grand Slam-chasing Wales a scare before going down 18-11 on Saturday.