The NFL Network's Rich Eisen broke down the importance of this matchup on Twitter:
Big 49ers/Seahawks Sunday Nighter: 49ers win, they win the West. If the Seahawks win, they clinch a spot and the West can still be won.— Rich Eisen (@richeisen) December 18, 2012
With both squads coming off big Week 15 wins, this will arguably be the most intriguing matchup on the slate for Week 16.
Where: CenturyLink Field, Seattle
When: Sunday, Dec. 23 at 8:20 p.m. ET
Live Stream: NFL Game Rewind
Spread: Seattle (+1) via Bet Online
I really struggled trying to pick this game, but I like San Francisco here.
If you watched their performance against the New England Patriots last week, I think you'll agree that the 49ers have established themselves as one of the best teams in football.
Not to take anything away from what Russell Wilson and the Seahawks have done, but I think the Niners are the better all-around team.
Over/Under: 39 (Bet Online)
This matchup will see two of the NFL's top three defenses, but I still like the over.
Both offenses average at least 25 points per game and the Seahawks have been putting up points in bunches.
Seattle won't be scoring like it has the past two weeks, but I expect this one to see more than 39 combined points.
Key Injuries (via USA Today)
WR Mario Manningham, shoulder, questionable
DE Justin Smith, arm, questionable
LB Ahmad Brooks, shoulder, probable
FB Bruce Miller, shoulder, probable
RB Marshawn Lynch, back, probable
WR Sidney Rice, foot, questionable
DT Alan Branch, ankle, questionable
CB Walter Thurmond, hamstring, questionable
Fantasy Big Plays
49ers: Frank Gore
Seattle's defense isn't easy to run on—it ranks 10th in the NFL—but Gore has already had success against it this season.
Gore rushed for 131 yards in Week 7 against the Seahawks, and with Seattle allowing more than 106 rushing yards per game, Gore is a solid option.
I'm not expecting a huge day, but if the 49ers are going to win on Sunday, they're going to have to utilize Gore to his fullest, which works out for fantasy owners.
Seahawks: Marshawn Lynch
The 49ers don't give up easy yardage or scores on the ground, but every once in a while, it happens.
Just ask Ahmad Bradshaw and the New York Giants.
Lynch is the second-leading rusher in the league, rushed for more than 100 yards when these two teams met in Week 7 and is coming off his eighth 100-yard effort this season.
It's hard to go against what Lynch is doing this season, so I'm not going to.
Key to 49ers Win: Keep Russell Wilson in the Pocket
Wilson has been so effective against opposing defenses this season when he escapes the pocket and makes plays on the run.
Whether he's throwing on the run or scrambling for a first down, Wilson has been a nightmare for opposing defenses.
That said, San Francisco has to keep Wilson in the pocket where it can get to him for sacks in order to win this game.
If they let Wilson run wild, it's going to be a long day for the Niners.
Key to Seahawks Win: Pound the Ground with Marshawn Lynch
The 49ers are exceptional at stuffing the run, but in order to open up play action and shots down the field, Seattle needs to run the ball with Lynch.
He's been a monster for Seattle all season.
Even if he isn't effective, he can serve as a decoy so that Wilson can make plays with both his arm and legs for Seattle.
Wilson has been great, but Lynch is the key to winning this game for the Seahawks.
Prediction: 49ers 21, Seahawks 20
It's going to be an extremely close game, but the Niners come out on top.
Colin Kaepernick and Frank Gore carry the offense to three touchdowns and San Francisco's defense does just enough to clinch the West.
For more information on this game, click here.
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