Alex Bruce and Grant McCann are the latest withdrawals from the Northern Ireland squad for Tuesday's World Cup qualifier against Portugal in Porto.
Republic of Ireland cap Bruce was in line for his Northern Ireland debut after receiving his first call-up.
Hull defender Bruce is ruled out by a groin strain while Peterborough's McCann has a knee injury.
Joe Dudgeon, Shane Ferguson, Martin Paterson and James McPake had already pulled out of Michael O'Neill's squad.
Bruce's Hull team-mate Dudgeon had also received his first call-up to the squad.
Chris Brunt and Jamie Ward were not named in the original squad because of injury.
O'Neill has already drafted Lee Hodson, Rory McArdle and Daniel Lafferty into his squad for the game but will not call up further replacements despite the withdrawals of Bruce and McCann.
Defender Bruce won his two Republic caps in friendlies in 2007 and 2008 so he is still eligible to represent Northern Ireland.
In recent years, several Northern Ireland-born players have switched allegiance south of the border.
These include Sunderland's James McClean, Everton duo Darron Gibson and Shane Duffy plus Stoke's Marc Wilson.
Bruce, the son of Hull manager Steve Bruce, was eligible for international football for Northern Ireland, the Republic of Ireland and England, where he was born.
He was called up by Northern Ireland Under-21s but opted to play for the Republic Under-21s instead.
Bruce then made his Republic senior debut against Ecuador in New York in 2007 and played against Poland a year later at Croke Park but losing his place in Giovanni Trapattoni's squad.
Northern Ireland squad
Goalkeepers: Roy Carroll (Olympiakos), Alan Mannus (St Johnstone), Michael McGovern (Falkirk)
Defenders: Aaron Hughes (Fulham), Ryan McGivern (Manchester City), Jonny Evans (Manchester United), Craig Cathcart (Blackpool), Lee Hodson (Watford), Daniel Lafferty (Burnley), Rory McArdle (Bradford City).
Midfielders: Chris Baird (Fulham), Steven Davis (Southampton), Oliver Norwood (Huddersfield), Corry Evans (Hull), Niall McGinn (Aberdeen), Pat McCourt (Celtic), Josh Carson (Ipswich)
Forwards: David Healy (Bury), Dean Shiels (Rangers), Kyle Lafferty (FC Sion), Will Grigg (Walsall)