Celtic left-back Danny Fox and Leeds winger Robert Snodgrass have withdrawn from the Scotland squad for the friendly against Japan on Saturday.
Former England Under 21 international Fox, who had been called up for the first time since switching allegiance, and Snodgrass join Rangers midfielder Kevin Thomson and Birmingham striker Garry O'Connor in pulling out.
Hearts left-back Lee Wallace has been called into the squad and Scotland boss George Burley is expected to draft more players in.
The Scottish Football Association soon confirmed that Aberdeen striker Lee Miller had also been called up.
The loss of Thomson and Fox for the trip to Yokohama came as no surprise after both missed Sunday's Old Firm clash through injury.
Thomson pulled out of his side's 2-1 victory after suffering pain in his knee while Fox sat out the Ibrox clash with a dead leg and a slight hamstring tear.
Snodgrass missed Leeds United's 0-0 draw with Charlton through injury.
O'Connor played 90 minutes for Birmingham during their 2-1 defeat by Burnley on Saturday and the reason for his withdrawal was not immediately clear as the SFA do not comment on injuries.
Although O'Connor played the full game at Turf Moor, he was limping badly in the final 10 minutes after taking a knock on the leg after Alex McLeish had made all three substitutions.
Sidelined: O'Connor (right) is also out
Burley may be hit by another withdrawal after Scott Brown visits a specialist over his ongoing ankle problem, which forced him to miss the start of the season.
The Celtic midfielder is due to see a Harley Street expert on Tuesday after continuing to suffer discomfort despite undergoing surgery in May.
Meanwhile, Wallace expressed his delight at his first call-up after initially being tipped to win a place in the original squad.
'I got a call from the SFA last night with the news and obviously I was very happy,' the 22-year-old told Hearts News.
'I am just happy to be involved. I was a lot more confident last season and hopefully this will help me keep improving as I'll be training with a lot of top-quality players.
'It may be a friendly but Japan are still a top team and of course I want to play.
'I know I wasn't in the original squad but I just accepted that and knew I just had to get on with my game and keep doing what I had been doing.
'I think the manager has seen me often enough and knows what I can do and I just want to go there and enjoy the experience.'
Miller won the last of his two caps during the 1-0 friendly defeat by Argentina in November last year.