Socceroos winger Mathew Leckie will be sidelined for around six weeks with a knee injury, while coach Graham Arnold promises to test players out against Mexico.
Leckie, 32, suffered a knock at training and has been ruled out of Sunday's game (AEST) at AT&T Stadium in Dallas, where centre-back Cam Burgess will make his debut.
Arnold also cast doubt over the World Cup hero's involvement in October's friendlies against England and New Zealand.
"He copped a knock. I'm not a physio or a doctor but it'll probably be around six weeks," Arnold said.
"It was an unintentional knock but it was just an accident. And these things happen in football, but Lecks is in good spirits himself.
"I would say today he won't be ready for October.
"The most important thing is his health and that Lecks is fine and I'm very apologetic to Melbourne City. It was a complete accident ... it was never intentional at all in any way.
"It was just one of those things that happened at training".
Leckie's injury opens the door for another attacker, with Arnold planning to swing several changes.
"We're playing against the No.12 nation in the world and it really gives me a chance to test players," he said.
"For me, it's about moving forward and seeing where we're at.
"It's going to be a great test mentally for the boys because obviously the crowd and the noise, because it's got a roof over it won't go out so it will be quite loud as well.
"It's an opportunity to try different things and the system won't change too much but roles will.
"The fact that we've got more youngsters coming through and coming in - it's a great opportunity to test them and give them this wonderful experience of playing this type of crowd and type of game and that'll hold us in good stead for the Asian Cup and moving forward.
Central defender Kye Rowles will shift to left-back with Burgess to start alongside Harry Souttar after impressing in camp and with Ipswich Town.
Left-back Jordan Bos (appendicitis) is sidelined while Aziz Behich has had limited minutes since joining Melbourne City.
"Aziz really hasn't played a match since June and the tempo will be quick at the start," Arnold said.
"I would have had full belief in Aziz as well but this gives me an opportunity to see how Kye can handle the left-hand side and perform on the left-hand side.
"They've got a right winger that doesn't like to defend too much and we just need to be careful there in transition that we look after that.
"Kye I've seen play so many times in a back three. So I've asked the question and that is simple: show me how you can play in a back four."
Arnold said former Central Coast winger Sam Silvera would debut at some point while there was "a good chance" Parma defender Alessandro Circati would get some minutes.