St Kilda vice-captain Dougal Howard will miss Sunday's clash against Fremantle due to the AFL's health and safety protocols.
It's a big blow for the Saints, who have called up Darragh Joyce as a replacement.
Howard's late withdrawal is one of several changes St Kilda are making ahead of the crunch clash in Perth. The club has already confirmed two other changes prior to today's news.
First-round draftee Nasiah Wanganeen-Milera has been guaranteed a proper debut after being the medical sub last week.
It's an exciting development for the Saints, who have also confirmed another debutant, with former Port Adelaide defender Jarrod Lienert named to take on the Dockers.
The pair are replacing Mitch Owens and Dean Kent, who were both omitted.
The club announced Howard's withdrawal on their website on Friday afternoon, however no further information is available.
Fremantle have also lost key players for the match, with David Mundy and Brennan Cox also ruled out through Health and Safety Protocols.
St Kilda vs. Fremantle isn't the only game impacted by COVID however, with star Sun Lachie Weller set to miss Gold Coast's clash with reigning premiers Melbourne on Saturday.
He will be replaced in the line-up by Rory Atkins.
It's a trend that's beginning to look like it will drag on all season; West Coast Eagles coach Adam Simpson announced on Friday that they will likely "lose 12 players from the Round 1 team" for their clash with North Melbourne this Sunday.
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Similarly, Carlton lost coach Michael Voss, as well as forward Jack Martin this week due to Health and Safety protocols.
The AFL had been prepared for COVID to wreak havoc with its season, ensuring all clubs could add supplementary players to their list in the event of players being ruled out due to COVID protocols.