The San Francisco 49ers haven’t exactly been blessed by the injury gods during the Kyle Shanahan era, and 2025 has been no exception. From quarterback shakeups to key starters missing time, it’s been a year filled with adversity. But in Week 16, the Niners might finally catch a break – and it comes in the form of a banged-up Indianapolis Colts team that’s down to its third quarterback.

Let’s start with the Colts’ quarterback room, which has been in a tailspin. Daniel Jones, who had been starting in place of the injured Anthony Richardson, went down with a season-ending Achilles tear in the first quarter of Sunday’s loss to the Jaguars.

And that wasn’t the only issue – Jones had already been playing through a hairline fracture in his left fibula. Tough as nails, but the body can only take so much.

That injury thrust rookie Riley Leonard into the spotlight. A sixth-round pick, Leonard made his first meaningful NFL appearance and finished 18-for-29 for 145 yards.

On paper, that’s serviceable. But the tape tells a more cautionary tale – he was lucky to escape without three interceptions.

The Colts’ offense still has firepower – Jonathan Taylor in the backfield, Michael Pittman Jr. out wide, Alec Pierce and tight end Tyler Warren providing support, plus a solid offensive line. But let’s be honest: the ceiling drops significantly when you go from a seasoned vet – or even a high-upside talent like Richardson – to a Day 3 rookie.

Speaking of Richardson, he’s technically eligible to return from injured reserve after suffering a broken orbital bone during warmups in Week 6. But as of now, he hasn’t been cleared for football activities. Jones’ injury might speed up that timeline, but even if Richardson suits up, there’s no guarantee he’s ready to handle the full weight of the offense.

This sets up a favorable situation for the 49ers. Shanahan’s squad has made a habit of feasting on inexperienced quarterbacks this season.

Just look at the track record: they held the Saints scoreless for nearly two full quarters, limited the Falcons and Giants to just 10 points each before garbage time, and kept both the Panthers and Browns in single digits. Defensive coordinator Robert Saleh has this unit humming, and against a rookie like Leonard – or a rusty Richardson – the Niners should be licking their chops.

Now, this isn’t a must-win game for San Francisco. But it’s the kind of matchup that can swing playoff positioning.

With the Seahawks and Rams still set to face off, the 49ers have a real shot to leapfrog one of them in the NFC standings. That makes Week 16 more than just another game – it’s a golden opportunity.

And after a season full of injuries and uncertainty, the 49ers won’t be taking that lightly.