The encounter on Saturday comes just over a month before the first Ashes Test of this summer's series gets under way at Trent Bridge. England are being widely tipped to retain the urn they have been in possession of since 2009 and Vaughan does not see Saturday's result having much impact on their confidence they will do so.
Yet he does think Australia will enhance their chances if they can emerge triumphant on Saturday. Speaking at Manchester's National Cycling Centre, where he was preparing for the PruProtect 'Chance to Ride' charity bike ride, Vaughan told Press Association Sport: "I don't think Saturday will affect England too much with regard to the rest of the summer, whatever happens."
He added: "But I think it could be a huge confidence booster for Australia if they go out and beat England on Saturday. I think it is what they need. There is a lot of change from their one-day side to their Test side, but there is a nucleus there that is set to be a part of that first Test on July 10."
Australia skipper Michael Clarke, who has been sidelined by a back problem, missed Tuesday's crushing 243-run warm-up defeat to India and is a doubt for Saturday's contest. Whether Clarke features or not, Vaughan - who led England to Ashes glory in 2005 - feels the outcome of the match will be of particular significance to the 32-year-old.
"He hasn't won that many games against England, particularly in the last couple of series," Vaughan, 38, said. "So with a view to whatever he can gain in terms of confidence and just a feel-good factor in and around his squad and group of players - for that sole reason, Saturday's game for Australia is a big one."
England go into the clash off the back of a 2-1 NatWest Series defeat to New Zealand - the first time they have lost a one-day international series at home since 2009. Vaughan has no doubt there is room for improvement in England's one-day side and that a win on Saturday would rejuvenate the mood around that team.
But he is keen to separate that from the Test side - who beat New Zealand 2-0 - and does not believe England's current situation is really comparable to the build-up to the 2005 Ashes, when he deemed shorter-form victories over Australia as crucial preparation from a mental point of view.
"We played Australia in 2004 in a Champions Trophy semi-final and beat them, and that was about eight or nine of each team that was going to be part of the Ashes - I felt that gave us a big lift," Vaughan said.
"Then when we hammered them in a Twenty20 match, again, I felt that it gave us a big lift. It was (important) for us because the Australian side at that time had dominated England for three Ashes series and many one-dayers."