The Giants are preparing for the worst, "confident" that the newly elevated vice-captain has torn the ACL in his left knee on Friday.
Green had to be helped off the field by trainers after trying to evade a tackle by forward Toby Bedford during an intra-club match simulation.
Reigning club best-and-fairest Green's leg was caught as he tried to change direction before Bedford laid his tackle.
The 25-year-old was slow to get off the ground and had attempted to get up without assistance, but was unable to bear weight on his left leg.
While the club is awaiting scans, Giants football boss Jason McCartney conceded the likelihood of Green avoiding an ACL injury was slim.
"Our medical team has assessed. Unfortunately, they're confident that it's an ACL injury," McCartney said on Friday.
"It's looking like a worst-case scenario, but we're fingers crossed, we're hoping for the best.
"He (Green) was in shock, like the coach, myself, and most of his teammates are trying to find out what was going on.
"He's reasonably upbeat, Tom, but it'll take a while to sink in, I'd imagine."
Green's inevitable absence is a hammer blow for GWS, with the All-Australian midfielder coming off a career-best season.
He and Finn Callaghan were in good spirits at a mid-week club briefing for Melbourne media.
Green had averaged a career-best 29.7 disposals and 8.5 clearances across 23 games last year, before the Giants' chase for a maiden premiership ended with a 19-point elimination-final loss to Hawthorn.
Luring 2021 Melbourne premiership player and fellow All-Australian onballer Clayton Oliver is set to prove even more important for Giants coach Adam Kingsley, given Green's prognosis.
They are already without veteran midfielder Josh Kelly (hip) and retired Callan Ward.
Oliver and Green had formed a formidable midfield partnership earlier on Friday before the latter went down.
"They'll get together at some stage, there's no doubt about it, but yeah, they were combining well," assistant coach Ben Hart said.
"Clayton's been a great addition to the footy club so far, and what he's doing on the field now, he's building strongly.
"It'll be a shame that we won't see them together if (the injury) gets confirmed, but he's doing some wonderful things as well."
Young gun Finn Callaghan was absent from training with soreness, but is expected to line up for their opening-round clash against the Hawks on March 7.
Hart said veteran onballer Stephen Coniglio - who will represent WA in Saturday's State of Origin clash - was finally fit and firing, with Harry Rowstan and 19-year-old Jack Ough.
The 32-year-old Coniglio was limited to 10 games last season due to a nerve issue in his glute.
"He's (Coniglio) had probably the best pre-season since I've been here, so in four years, and looking really strong," Hart said.
"He's got himself back to a level of using his speed."
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