Travis Head, the matchwinner in the first of the three-game series at Southampton on Wednesday, has been tasked with the captaincy duties for the first time in his career.
The left-hander will be charged with leading from the front straight away at the top of the order after Australia lost the toss and were put in to bat on Friday evening.
"Mitch is a bit sick at home," reported Head at the toss, admitting that the skipper's illness and the absence of injured pacer Xavier Bartlett meant it was "all hands on deck" for the Australians, with the prospect of a series win in their sights.
Marsh's absence meant a recall for exciting young batter Jake Fraser-McGurk, who was dropped for the opener.
Josh Hazlewood, impressive in Southampton, has been rested, presumably to protect him after a recent calf niggle, with seam bowling allrounder Aaron Hardie and spinning allrounder Cooper Connolly coming into the side that bats really deep.
Overnight scans revealed Bartlett had suffered a side strain in the first game, and he will not play in Sunday's final T20 in Manchester either, with Ben Dwarshuis joining the squad for the Old Trafford game.
England made a surprise change too for their must-win match, deciding to wrap up their brilliant but injury-prone strike bowler Jofra Archer in cotton wool while bringing in Brydon Carse.
Teams
England: Phil Salt (capt), Will Jacks, Jordan Cox, Liam Livingstone, Jacob Bethell, Sam Curran, Jamie Overton, Brydon Carse, Adil Rashid, Saqib Mahmood, Reece Topley.
Travis Head (capt), Matt Short, Jake Fraser-McGurk, Josh Inglis, Marcus Stoinis, Tim David, Cameron Green, Aaron Hardie, Cooper Connolly, Sean Abbott, Adam Zampa.
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