GWS will be without important duo Finn Callaghan and Harry Perryman for their Opening Round clash on Saturday against Collingwood, according to AFL.com.au.
Perryman - who's been tending to hamstring troubles - was officially ruled out of the match on Tuesday and will be sorely missed for the Giants in the defensive half, joining Isaac Cumming (quad) on the sidelines.
However, his absence may open the door to veteran Nick Haynes as Adam Kingsley's men look to bolster their backline, while Lachie Whitfield could be considered to help fill the void.
Youngster Callaghan - who's quickly becoming a star of the competition - has failed to overcome a shoulder issue despite having an impressive summer.
The 20-year-old was set to divide his time through the wing and in the midfield but will now eye off a return in Round 1 against North Melbourne.
Darcy Jones (knee) - who missed last year due to an ACL injury - is likely to be available for selection in Round 3, as Cumming will be on a similar timeline.
As for the other Giants' injury concerns, Braydon Preuss (back), Adam Kennedy (knee), Phoenix Gothard (illness) and James Leake (quad) will likely miss the opening two months of the season.