Richmond's No.1 draft pick Sam Lalor might need surgery and Nik Cox's concussion history has also ended his AFL season.
Sydney also received bad news on Monday, with forward Joel Amartey likely out for the rest of the season with a high-grade adductor strain, and Tom Papley sidelined for two to three weeks with a hamstring injury.
Lalor re-injured his left hamstring only a couple of minutes into his return on Saturday against Geelong, with the Tigers confirming on Monday his season is over.
The AFL's concussion panel, which last month recommended West Coast defender Jeremy McGovern should retire on medical grounds, gave Cox hope he will resume his playing career.
While Cox will not play this year due to his concussion problems, the panel gave him a pathway to make an AFL comeback after meeting him last month.
Lalor has succumbed to a left hamstring injury for the third time, previously injuring it before he was drafted last year and then in the May Dreamtime at the 'G match against Essendon.
The Tigers were cautious, holding him back for a week, but he limped off GMHBA Stadium after tackling Tom Atkins early in the first quarter.
"We are all devastated for the young man, and I am sure our fans are too," Richmond high-performance manager Ben Serpell said.
"The injury mechanism here for Sam this time was very different to his original injury mechanism.
"He sustained the injury in a tackle. I think anyone who throws their body at the game as he did, and credit to him for doing that, is going to put their body at some risk irrespective of their injury history."
Given Lalor's terrible injury history, he might undergo surgery on the hamstring.
"We are a bit concerned about the integrity of the hamstring structure," Serpell said.
"As part of that we will consult a few surgeons over the next little while to see if there is some surgical intervention available for us."
Meanwhile, Cox is upbeat about his future after being told by the concussion panel he can resume his AFL career.
"While I'm disappointed that I won't return to the field for the remainder of the 2025 season, this time away from the game will be used to focus fully on my health, recovery, and building the strongest possible foundation heading into pre-season," Cox said.
"I've learned a lot about myself over the past few months, and I'm more motivated than ever to get back to doing what I love.
"My focus now is on continuing to work closely with specialists and the club to make sure I'm in the best place physically and mentally to return to football."
The Swans, who beat Fremantle on Sunday, confirmed their injury news in a brief statement on Monday night, saying Amartey would be out for eight to 12 weeks.
With seven home-and-away rounds left before the pre-finals bye, Amartey could be fit in time for the start of September, but it would take a remarkable run by Sydney to reach the play-offs.
They are currently 10th after winning three of their past four games, but are still three wins off eighth.