Geelong has already drawn a thick red line through four key players ahead of Friday night's clash, the result of which could have huge ramifications on the clubs' finals hopes.
For the first time this season, and the first time since crossing from Adelaide, Patrick Dangerfield will miss after accepting a one-match ban from the Match Review Panel on Wednesday.
He'll join Nakia Cockatoo (hamstring), Daniel Menzel (general soreness) and Steven Motlop (managed) on the sidelines for the crucial Round 20 contest at Kardinia Park.
Geelong coach Chris Scott said Dangerfield's absence leaves a big hole to fill but his young, new-look outfit (Scott expects up to nine players who played in the preliminary final against Sydney to miss) brings an air of excitement and possibility.
"It's going to be a challenge," Scott said on Wednesday.
"I don't subscribe to the theory that you just take out one of the best players in the competition and replace him with a youngster and all is well.
"It's going to make it more challenging for us, but not impossible.
"We have a group of players who are looking forward to continual improvement and sometimes these opportunities allow other to step up.
"It is a new team and that's daunting on one level but exciting on another."
A win for either side is important to their finals hopes. Geelong, sitting second and only a game behind league leaders Adelaide, will be keen to lock away a top-two spot while a win or loss for Sydney could mean the difference between tightening its grip on a top-eight spot or dropping as low as ninth after the weekend's round.
Geelong has won only one of the past five encounters against Sydney, but will breath a little easier knowing the next contest is at its happy hunting ground of Kardinia Park.
The Cats have got the better of John Longmire's men in 10 of the past 12 matches by an average of 30 points.
Last year's result however went the way of Sydney when Kieren Jack, in his 200th match, led his side to an emphatic win.
That was incidentally the last time Geelong has lost at Kardinia Park.