Ladell Betts and Chad Rinehart suffered season-ending injuries in Sunday's game against the Dallas Cowboys.
They both were placed on injured reserve on Monday, the team announced.
Betts suffered knee ligament tears in both his ACL and MCL during the first quarter of the game and had to be carted into the locker room.
He was fitted for a soft cast and watched the rest of the game from the sidelines.
"We lost Ladell Betts for the season," head coach Jim Zorn said. "He's definitely down...I don't expect to have him back."
Rinehart suffered a fractured fibula in the third quarter and was carted off the field.
He had surgery on the fibula on Monday afternoon.
"They are putting in a plate and screws to support his fibula," Zorn said. "He'll be on injured reserve."
In the Cowboys game, Betts was replaced in the lineup by Rock Cartwright and Rinehart was replaced by rookie Edwin Williams.
Meantime, fullback Eddie Williams was placed on injured reserve on Monday. He suffered a fractured fibula in practice last Friday.
Williams had surgery over the weekend. He was seen at Redskins Park on Monday wearing a cast around his ankle.