Already missing skipper Trent Cotchin, Richmond must muscle up to fellow AFL flag favourites West Coast without first-choice ruck Toby Nankervis and breakout 2019 campaigner Sydney Stack.
Nankervis was limited to jogging laps during the Tigers' main training session Punt Road Oval on Friday.
He was subsequently withdrawn from the Richmond team, and will join Cotchin and long-term absentee Alex Rance on the sidelines as big guns unable to fire in the clash.
Stack's omission is a shock given he has been spoken of as a Rising Star rival to Carlton's Sam Walsh.
But coach Damien Hardwick has decided to keep Jack Ross in his 22, dropping Stack to make room for returning superstar Dustin Martin.
"It is good to get good players back," Hardwick said of Martin.
"It was a bit touch and go last week but with the amount of work he's put in training this week it was always going to be an easy decision to make so we look forward to welcoming him back."
Ivan Soldo has been chosen to replace Nankervis.
In contrast to Richmond's two changes, West Coast will field the same 22 that beat Adelaide last week.
GWS Giants, which faces a red-hot Western Bulldogs, have made five changes for their clash in Sydney.
Josh Kelly has got the all-clear to resume after a six-week absence, while Matt de Boer, Harry Himmelberg and Aidan Corr also return.
Zach Sproule, a tall forward from Albury, will make his debut.
Brett Deledio and Jeremy Cameron are out with injury, while Jackson Hately, Dawson Simpson and Aiden Bonar have all been dropped after the Giants' lacklustre loss to Hawthorn last week.
The Western Bulldogs are unchanged after their 104-point demolition of Essendon.
As foreshadowed through the week, Jarryd Roughead has been named in Hawthorn's side to face Gold Coast on Sunday in an otherwise largely inconsequential affair.
Returning alongside Roughead is a trove of experience - fellow flag-winners Jack Gunston and Ben McEvoy as Daniel Howe, Mitchell Lewis and James Cousins drop out.
Australian Associated Press