Number eight David Denton and wing Lee Jones will miss Scotland's summer tour to Australia, Fiji and Samoa due to injury.
Denton has damage to his left ankle ligaments, while his Edinburgh team-mate Jones has a fractured right shoulder blade.
The duo join Jim Hamilton in missing the tour after the Gloucester lock received a seven-week ban from the Rugby Football Union following a brawl with London Irish hooker David Paice during the Aviva Premiership game between the clubs on May 5.
Denton and Hamilton were ever-presents during the Six Nations, while Jones only missed the final match in Italy due to concussion, and their absences are blows for a Scotland side seeking to arrest their worst run since 1998.
Scotland go into the Test with Australia on June 5 seeking to end a seven-match winless sequence, before playing the NSW Waratahs on June 10 and Tests against Fiji on June 16 and Samoa a week later.
Head coach Andy Robinson is poised to name his squad on May 16.
Jones' absence can be compensated for by the inclusion of Edinburgh's flying Dutch winger Tim Visser, who come June 12 will be eligible for Scotland on the grounds of three years' residency.
Missing Denton will stretch Scotland's back-row resources, with Saracens' Kelly Brown already absent after he dislocated his fibula in January, while Hamilton's indiscretion means he returns behind World Cup captain Alastair Kellock in the second row order.
Scotland team doctor James Robson said: "Lee suffered the fracture in the Heineken Cup semi-final loss to Ulster last month.
"Injuries of this nature typically resolve over the course of six to eight weeks, so he will not be available for the tour.
"David sustained the ankle injury in the final game of the league season against Treviso last weekend and subsequent scanning of the joint revealed damage to the ligaments.
"Following consultation with John McKinley, the ankle specialist at Spire Murrayfield Hospital, David will not require surgery but will now embark on a prolonged period of rehabilitation which will rule him out of the summer tour.
"His estimated return would be between eight to 10 weeks."