Dion Prestia and Jack Riewoldt are both facing stints on the sidelines as Richmond count the cost of a painful opening-round defeat to AFL rivals Carlton.
The premiership pair were hurt during the 25-point defeat at the MCG on Thursday night, when the Tigers coughed up a 20-point lead during a stunning final-quarter capitulation.
Riewoldt played out the match with a suspected fractured thumb, while Prestia left the field with a hamstring injury before halftime.
The pair are almost certain to miss the round-two meeting with GWS in 10 days' time.
Unlucky midfield star Prestia has been plagued by hamstring issues in the past and has managed just nine games in each of the past two seasons because of a long list of injury setbacks.
"It's just disappointing after he's had as good a pre-season as he's had," Richmond coach Damien Hardwick said.
"He's so important to the way we play and I feel like he's barely played in two-and-a-half years.
"He had 10 touches in the first quarter and, lo and behold, we were up and going, and then he goes out.
"He's a significant loss, big loss. I just really feel for the kid.
"He was really disappointed and I'm really disappointed for him because we want him on the field.
"It's a challenging stage for him."
Riewoldt spent time in the change room with medical staff early in the match and returned with strapping around his thumb.
The key forward did not have his usual impact, finishing with one goal from just six disposals.
Hardwick said Riewoldt may require surgery.
"We think Jack might have fractured his thumb, so we'll have scans to confirm that," Hardwick said.
"That's why he went off early and probably struggled to hold the ball a little bit tonight.
"We didn't fare too well."