Sources: San Francisco 49ers QB Jimmy Garoppolo, TE George Kittle to miss multiple weeks

SANTA CLARA, Calif. -- In a season full of seemingly nonstop, devastating injury news, the San Francisco 49ers might have taken their two biggest hits, as sources told ESPN's Adam Schefter on Monday that quarterback Jimmy Garoppolo and tight end George Kittle are expected to miss extended time.

For Garoppolo, the aggravation of his high right ankle sprain that took place in Sunday's 37-27 loss to the Seattle Seahawks is expected to keep him out for a minimum of six weeks and possibly longer if it requires surgery, a source told Schefter.

Despite initial optimism that Kittle didn't have any fractures in his foot, further testing revealed a broken bone that will cost him about eight weeks, a source said. With eight games and a bye remaining, Kittle's season could be over.

Garoppolo and Kittle both departed Sunday's game in the fourth quarter. Garoppolo appeared to tweak his ankle earlier in the game and play through it, but he was removed with 14:02 remaining. He limped to the locker room after going 11-of-16 for 84 yards with an interception for a passer rating of 55.2.

Nick Mullens replaced Garoppolo and went 18-of-25 for 238 yards with two touchdowns for a passer rating of 128.4. With Garoppolo out for extended time, Mullens will step back into the starting role, a job he filled when Garoppolo missed two games with the ankle sprain earlier this season. C.J. Beathard will serve as Mullens' backup.

Mullens said Sunday that he'd be prepared to step in for Garoppolo longer term if need be.

"Any time you can get out there and bounce back from my last start, it's definitely going to create confidence," Mullens said. "The biggest thing I've learned just going through it all is that the NFL is tough. It's all about what you do next. That's why I tell myself pretty much every day, 'It's all about what you do next.' No matter if it is good or bad, it's all about what you do next."

Kittle's foot injury happened less than two minutes after Garoppolo left when he leaped to haul in a 25-yard pass from Mullens. Kittle made the catch but landed awkwardly and hobbled to the sideline soon after, then headed to the locker room for further evaluation.

Coach Kyle Shanahan said after the game that initial X-rays on Kittle showed no breaks but that further tests would be needed to confirm that on Monday. Kittle, who signed a five-year, $75 million contract extension during training camp, missed two games earlier this season with a sprained MCL in his left knee.

Ross Dwelley replaced Kittle against the Seahawks and caught a touchdown from Mullens, though the Niners could be getting tight end Jordan Reed back from a sprained knee soon in the effort to help replace Kittle.

"Hoping for Jordan Reed this week, but I'm not sure right now," Shanahan said Sunday.

Kittle and Garoppolo are only the latest additions to a lengthy Niners injury list that includes other prominent players such as defensive end Nick Bosa (torn ACL), running back Raheem Mostert (high ankle sprain), receiver Deebo Samuel (strained hamstring) and cornerback Richard Sherman (strained calf).

Even before Kittle and Garoppolo likely land on injured reserve, the 49ers had the highest cap value of players on injured reserve this season at $54.2 million. In eight games, the Niners have had three different leading passers, four different leading rushers and four different leading receivers.

All of that attrition has taken a toll in the Niners' locker room.

"It still hurts," fullback Kyle Juszczyk said. "Even though it seems to happen just over and over again, guys dropping every game, it still hurts each time."

The 49ers (4-4) won't have much time to dwell on their latest injuries. They are slated to host the Green Bay Packers (5-2) on Thursday night.