But the surging Hawks insist they can cover the absence of Frost down back when they travel to face Port Adelaide in Friday night's semi-final.
Ruckman Lloyd Meek said he was feeling for Frost, who has played every game this year, but the Hawks had full faith in whoever comes in.
"It's heartbreaking for us," he said on Monday.
"We're a tight-knit group, and he's played such a huge role for us this year.
"But similar to other big injuries we've had, another man will step in.
"Finn Maginness, Josh Ward and Harry Morrison, they've been a little bit on the fringe, but they all had massive games on Friday night."
Jarman Impey plays alongside Frost in defence and will miss his towering presence, which allows captain James Sicily to intercept across halfback.
Jarman Impey feels for injured fellow defender Sam Frost. (Linda Higginson/AAP PHOTOS)
But like Meek, Impey believes Hawthorn can continue their winning ways and progress to their first preliminary final since 2015.
"Very sad that Sam went down on the weekend and he's not going to play this weekend," Impey said.
"The boys are absolutely feeling for 'Frosty' because he deserves to be out there running alongside us this weekend.Â
"I think anyone could step in and play a role for us at the moment, so that's very exciting."
Hawthorn won't be short on key defenders next year if there is an injury with West Coast's Tom Barrass and St Kilda's Josh Battle set to join the club during the trade period.
"Being able to get to this position at the end of the year (in finals) and being able to have some new players coming in as well is very exciting,"Impey said.
"It just shows that there's people that want to be a part of what we're trying to create and what we're trying to build so very excited that we can hopefully get a few more to the list and make us stronger for the future."
Midfielder Will Day is set to join Frost in being ruled out of facing the Power as he struggles to recover from a collarbone injury suffered in round 23.
Will Day is also set to miss the Hawks' semi-final against Port Adelaide. (Morgan Hancock/AAP PHOTOS)
Fellow midfielder Cam Mackenzie was ruled out of taking on the Bulldogs after hurting his hamstring at training and remains in doubt for the match at the Adelaide Oval.
The Hawks, who finished seventh after the home-and-away season, will start as warm favourites to beat the third-ranked Power, who are coming off an embarrassing 84-point qualifying final smashing by Geelong.
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