The San Francisco 49ers (5-7) just can't catch a break this season.

Last night's snowy contest in Buffalo resulted in San Francisco's second straight 25-point loss. The Niners are now a far cry from playoff contention, owning +1400 NFC West odds. Matters went from bad to worse when Christian McCaffrey exited Sunday night's game with a non-contact knee injury and never returned.

CMC has been a total headache for fantasy football managers this season. With five weeks left in the regular season and the fantasy playoffs looming, how should you handle the fallout of McCaffrey's injury -- namely how it relates to Jordan Mason and Isaac Guerendo? Let's dive in.

(UPDATE: It has since been announced that Mason will also go on IR due to a high-ankle sprain. This makes Guerendo the top priority on waiver wires as the only healthy back currently on the active roster. He'll likely lose some passing-game work to Deebo Samuel and Kyle Juszczyk, but the early-down work will immediately make Guerendo a startable and desirable fantasy option.)

Christian McCaffrey's Knee Injury Timeline

McCaffrey missed the first nine weeks of the season due to a calf/Achilles injury. He made his season debut in Week 10 and completed three straight starts -- albeit with limited productivity, amassing just 3.5 yards per carry.

He started to look a bit more like himself last night with a powerful 19-yard run, but he slid to the ground with a non-contact injury later that drive. CMC was officially ruled out by halftime for what was later revealed to be a PCL injury. Head coach Kyle Shanahan stated the injury is a "potentially" season-ending blow for McCaffrey.

Considering McCaffrey's injury history this year and the typical timeline for PCL injuries, it's likely that we've seen the last of CMC this regular season. The 5-7 Niners might need to win out to achieve a postseason spot, which leaves zero room to ease McCaffrey back in should that even be a possibility.

Jordan Mason's Fantasy Football Outlook

With CMC out of the fold, Jordan Mason has jumped back onto our fantasy radar.

Mason is undoubtedly situated to lead San Francisco's backfield the rest of the way. He played 78.6% of the snaps in his first four games of the season, logging a minimum 73.3% snap rate in this span.

In Week 5, Mason was reduced to a 66.7% snap rate while Isaac Guerendo carried the rest of the load in a competitive one-point loss. Although San Fran opted to scale him a bit back in that one, it checks out considering Mason was handling a massive 22.8 carries through his first four. Guerendo went on to out-snap Mason 20.0% to 9.1% in three full games alongside CMC, but that garbage time sample isn't particularly relevant.

Last night reminded us what we should expect from Mason sans CMC. Mason played 51.1% of the snaps despite McCaffrey handling 25.5% of the snaps. Guerendo was at a 23% snap rate. Mason was also evaluated for a concussion and missed out on playing time due to the blowout. In turn, we can probably expect Mason to get near -- and maybe even match -- the snap rates he was rocking with in his first four games this campaign.

That's great news considering Mason's usage through those first four resulted in 447 rushing yards and three touchdowns in that time. He hit the century mark in rushing yards in all but one of those games. In the five contests prior to a Week 6 shoulder injury, he handled a 74.3% red zone rush share.

In terms of weekly finishes, Mason finished as the RB3, RB8, RB23, RB4, and RB27 in his relevant sample without McCaffrey. Even if Mason doesn't reach quite the same echelon of usage going forward, we should still expect him to re-enter this tier, so it's no wonder why he's such a commodity in fantasy moving forward.

Here's a look at San Francisco's remaining matchups. Schedule-adjusted rush defense ranks are through Week 12.

The Niners will draw four matchups against teams that rank in the top 15 for most FanDuel points allowed to RBs. This coming week, they'll face a 17th-ranked schedule-adjusted rush defense. San Fran is favored by 3.5 points and has a 24.5 implied team total against the Chicago Bears, so Mason already pops out in DFS at his $8,000 FanDuel salary.

Isaac Guerendo's Fantasy Football Outlook

Guerendo won't command much attention in DFS for the time being, but he's worth monitoring as a potential waiver add.

Guerendo popped off for 99 yards as well as 85 yards and a score in the two games that Mason left early due to a shoulder injury. Guerendo has delivered when handed the opportunity and is generating 5.9 yards per carry this season.

That's notable considering the injury bug going around in San Francisco. There's a chance we could see the Niners scale back Mason's usage in order to preserve the backfield for the remaining five games. While I'm high on Mason based on what we saw on Sunday night, there's a possibility the Niners opt for the Week 5 route where Guerendo took 33.3% of the snaps.

It wouldn't be shocking to see the 49ers mix it up down the stretch since they are undermanned and fighting for their season, so Guerendo is one of the top players to monitor moving forward. Week 14's date with the Bears should be telling.

New to FanDuel Sportsbook? You’ll receive $150 in Bonus Bets if your first bet of $5+ wins! See here for full terms and conditions. Learn about today’s other offers at FanDuel Sportsbook Promos.

Interested in playing NFL DFS? Head over to FanDuel’s daily fantasy football lobby to see all the offerings for this week's slates.

Sign up for FanDuel Sportsbook and FanDuel Daily Fantasy today!

The above author is a FanDuel employee and is not eligible to compete in public daily fantasy contests or place sports betting wagers on FanDuel. The advice provided by the author does not necessarily represent the views of FanDuel. Taking the author's advice will not guarantee a successful outcome. You should use your own judgment when participating in daily fantasy contests or placing sports wagers.