Defender Adam Kennedy has undergone a shoulder reconstruction on Tuesday after injuring himself during last Thursday's training session.
Kennedy has suffered the same injury as ruckman Braydon Preuss, who successfully underwent his own shoulder reconstruction last Thursday.
The pair will be sidelined for four-to-five months and are expected to return to the field mid-year.
Zippy forward Brent Daniels is also in doubt for round one after suffering a hamstring injury in the same session.
Daniels is expected to miss approximately six weeks with the injury.
GIANTS Head of Medical Cullan Ball said:
“It’s really unfortunate for Adam but we know he’ll attack his rehabilitation with his usual diligence and professionalism.
“He’ll rehab alongside Braydon who’s surgery went really well last week and he’s already back in at the club.
“Brent’s suffered a fairly significant hamstring injury so we’ll build him up slowly to be ready in the early parts of the season.”
Captain Stephen Coniglio is expected to play this week’s practice match against the Swans at GIANTS Stadium after suffering a concussion two weeks ago.
Coniglio will be more than 12 days post-concussion - the new minimum time on the sidelines for a concussion - by Saturday’s game and has passed a fitness test on Wednesday.
Forward Bobby Hill and draftee Ryan Angwin will be unavailable for Saturday’s match, having both also recently suffered concussions.
Defender Phil Davis is also unavailable for Saturday’s match but has returned to full training following knee surgery post-season last year.
He’s expected to be a test for the AAMI Community Series the following weekend.
Meanwhile, Lachie Whitfield has returned to the club as he recovers from a bruised liver.
“Lachie’s back at the club and starting to build up his training,” Ball said.
“It was a fairly significant injury so he’ll continue to progress as he’s medically cleared to do so.
“He’ll miss the practice match and AAMI Community Series and we’ll see how he’s tracking ahead of round one.”
The GIANTS will take on the Swans in a match simulation practice match at GIANTS Stadium this Saturday before the AAMI Community Series the following weekend.
The GIANTS begin their 2021 season with a round one clash against St Kilda at GIANTS Stadium on March 21.