Star Richmond forward Tom Lynch is set for a lengthy stint on the sidelines after fracturing his right foot in Saturday's five-point loss to the Western Bulldogs.
Lynch will undergo surgery, and the Tigers will reassess the injury after that before putting a timeline on his return.
Jack Graham is set to miss several matches after injuring his hamstring.
Lynch kicked two goals in the opening term against the Bulldogs before sustaining the foot fracture in the second quarter.
The 30-year-old clearly struggled after that, tallying just two disposals in the second half.
He is also facing a minimum three-match suspension after being sent straight to the AFL Tribunal for his heavy bump that concussed Western Bulldogs defender Alex Keath in a marking contest.
Lynch's injury is a huge blow to Richmond's hopes of becoming a genuine premiership threat this year.
The key forward kicked 63 goals last season in his best return since joining the Tigers at the end of 2018, and his absence will place extra pressure on veteran Jack Riewoldt.
Riewoldt was surprisingly rested against the Bulldogs, and is set to return for next Friday's Gather Round clash with Sydney at Adelaide Oval.
Tigers coach Damien Hardwick said it was important to rest 34-year-old Riewoldt and the club's other ageing stars, much like Geelong did last year on the way to the premiership.
"We've got guys who are mid 30s, so they're not going to be able to play every game, and we don't want them to play every game," Hardwick said.
"The players have got a good understanding of that. I think it's one thing our industry haven't got their head around.
"We want to keep the good players going for longer, so it means they're not going to play 22 games.
"The game's as hard as it has ever been. So we can sit there and keep trying to do it, and we can keep getting injuries.
"Or we can sit there and try to manage those guys and try to get them right for hopefully the pointy part of the season."
Richmond sit outside of the top eight after opening their season with a win, two losses and a draw.
