Rangers centre-back Russell Martin and Celtic left-back Kieran Tierney will miss Scotland's friendlies against Costa Rica and Hungary through injury.
Celtic's Jack Hendry has been called up as a replacement.
Martin, capped 29 times, picked up a knock in Rangers 1-0 defeat to Kilmarnock on Saturday.
Tierney, 20, has had a calf problem since last weekend's 3-2 win over Rangers and missed Sunday's 0-0 draw with Motherwell.
Celtic manager Brendan Rodgers told BBC Scotland: "We gave him every chance this week. He won't go with the international team."
Hibernian midfielder Dylan McGeouch is an injury doubt after missing his side's 1-1 draw with St Johnstone on Friday with a groin strain.
Head coach Neil Lennon is happy to allow McGeouch to be assessed by the Scotland medical staff.
But Rodgers says Tierney will not be involved in Friday's game against Costa Rica at Hampden Park, or the trip to face Hungary in Budapest four days later.
"He needs to just get right over these next few weeks and hopefully be back ready after the international break," Celtic's manager added.
"It's a slight tweak in his calf towards the end of the game last weekend, but that puts him out for this game and hopefully he can recover over the international break."
Scotland have plenty of cover at left-back, with Wolverhampton Wanderers' Barry Douglas being called up for the first time and Liverpool's Andy Robertson also in good form.
Tierney had been used at right-back by previous national head coach Gordon Strachan.
However, successor Alex McLeish said he would only choose that option as an emergency and was considering playing Tierney in central defence, where he has played for his club.
Hendry has made four appearances for Celtic since signing from Dundee during the January transfer window, and the 22-year-old has yet to be capped for his country.
Goalkeepers: Jordan Archer (Millwall), Allan McGregor (Hull City) Jon McLaughlin (Hearts)
Defenders: Barry Douglas (Wolves), Grant Hanley (Norwich City), Scott McKenna (Aberdeen), Charlie Mulgrew (Blackburn Rovers), Callum Paterson (Cardiff City), Andrew Robertson (Liverpool), Jack Hendry (Celtic).
Midfielders: Stuart Armstrong (Celtic), James Forrest (Celtic), Tom Cairney (Fulham), Ryan Fraser (Bournemouth), Kevin McDonald (Fulham), Kenny McLean (Aberdeen), Dylan McGeouch (Hibernian). John McGinn (Hibernian), Callum McGregor (Celtic), Scott McTominay (Manchester United), Jamie Murphy (Brighton & Hove Albion, on loan at Rangers), Matt Phillips (West Bromwich Albion), Matt Ritchie (Newcastle United), Ryan Christie (Celtic, on loan at Aberdeen)
Forwards: Oliver McBurnie (Swansea City, on loan at Barnsley), Jason Cummings (Nottingham Forest, on loan at Rangers)