Midfielder Collison (knee) and defender Collins (groin), a recent signing from Aston Villa, both fell out of the reckoning for the Parc-y-Scarlets clash, with Joel Lynch and Robert Earnshaw called up as their replacements.
Collison, 23, has been dogged by knee problems in recent seasons, while Collins, 28, has not played for his country since the Euro 2012 qualifying defeat against England in March 2011.
The pair have come in for criticism from former Wales international Mickey Thomas, but Coleman sprang to their defence when questioned on their absence.
"I have seen Mickey's comments, he is paid to give his opinion but I don't agree," Coleman said
"Jack Collison has had a serious knee problem, not for six months or 12 months, but for two or three years.
"He has got through games when maybe he shouldn't have because he wants to play, and he has even come away with Wales when maybe he shouldn't have.
"But we know Jack very well, he has a lot of desire for football, he loves to come and play for Wales and we love having him play for Wales, but physically he cannot do it.
"He has not kicked a ball since the play-off final, where he ran himself into the ground and had a big impact. He has not done a lot since and he needs a rest.
"We left him out of the Mexico game as he had the play-off final coming up and he had played a lot of football, I think it was around 30 games for West Ham, and he is always trying to maintain his knee problem. Now he needs a complete rest.
"I will take some of the responsibility for naming him in the squad and then getting information on him.
"But if he is not right and he cannot play for West Ham, how can he play for us?
"James Collins, we think, has a hernia problem which may need surgery, he can't play. He limped off in a friendly in Portugal for West Ham so he can't play.
"They are two players who will always be in my thoughts and be there or thereabouts when I am naming my squad."
Wednesday's fixture is the final chance for Coleman to prepare for the World Cup qualifiers which begin against Belgium in Cardiff next month, and the former Fulham boss believes the fixture is the ideal test for his side before the serious business gets under way.
"This is an important game against a very good team," he said.
"People say they have not won for five games but look at the sides they have lost against. France, Mexico, Brazil, these are some of the best sides they have been up against.
"They are ranked in the top 30 and it is a good game for us ahead of the Belgium game next month."