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Stade Francais full-back Southwell has not recovered from a facial injury he suffered in the defeat to Wales while Northampton Saints centre Joe Andbro will be absent after suffering concussion in his side's defeat to Bath on Saturday.
Toulon full-back Lamont also picked up a knock whilst playing for his club-side on the weekend and will miss the game through a leg injury.
"We have made the decision now that all three of our injured backs will miss this weekend's international, so that brings clarity to our preparations," said Scotland coach Andy Robinson.
"We wish all of them a speedy recovery. Our medical staff will continue to treat and monitor our injured forwards.
"Everybody was hurting after the display against Wales, but we must now focus on the challenge that Ireland bring and there's absolute determination to bounce back against them at Murrayfield on Sunday."
