Inexperienced Matt Flynn will be recalled to combat Demons premiership pair Max Gawn and Luke Jackson after Preuss was rubbed out for striking Fremantle's David Mundy.
The incident occured during the Giants' 34-point defeat at Optus Stadium last week, which left them with a 1-3 record ahead of Saturday night's trip to the MCG.
Preuss' suspension is his second in a matter of weeks and comes after he missed all of last season - his first at GWS after stints at North Melbourne and Melbourne - through injury.
Giants coach Leon Cameron said Preuss had spoken to his teammates this week, admitting he had let them down.
"We're not going to sugar-coat it; I'm disappointed and I've spoken to him about it," Cameron said.
"I'm loving what he's starting to show as a footballer but equally you want him out on the park more."
Flynn, who has played just 14 senior games, will be supported by either five-gamer Kieren Briggs or key defender Lachlan Keeffe.
"Keeffe did it a few weeks ago with Preuss and we were really rapt but equally Briggsy's starting to build his fitness base on the back of an interrupted pre-season," Cameron said.
"Clearly you need to take two big men in the department to combat Gawn and Jackson.
"Their combination, everybody knows how good it is.
"It's an opportunity for our young fellas or Keeffe as our second ruck to take it right up to them."
Cameron said Lachie Whitfield is available to take on Melbourne despite hurting a knee during the Fremantle clash.
But there is still doubt over star defender Nick Haynes, who missed that game with an ankle injury.
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