James Collins, Paul Dummett and Lee Evans have become the latest withdrawals from an already-depleted Wales squad.
Chris Coleman's men are due to face Bosnia-Herzegovina and Cyprus over the coming week as their Euro 2016 qualifying campaign, which started with a 2-1 win in Andorra last month, continues.
Wales had already been weakened by injuries to key midfielders Aaron Ramsey and Joe Allen, but will now have to contend with a further trio of pull-outs.
West Ham defender Collins has been forced out with a groin problem picked up in training on Friday, while Newcastle United's Dummett has a muscular issue.
Wolves' Evans, who could have made his international debut, has failed to recover from a hamstring injury and revealed his disappointment at missing out.
"Disappointed to have to head home from the Welsh camp! Hopefully my time with Wales will come again," he wrote on Twitter.
Coleman has called up Cardiff City's Declan John and Joe Walsh of Crawley Town to cover for the absences.