After being thoroughly trounced by the New England Patriots last week by a score of 52-28, things don't get any easier for the Buffalo Bills, as they have to travel across the country to take on the San Francisco 49ers.
The 49ers put a beating on another AFC East opponent last week, embarrassing the New York Jets by a score of 34-0.
With the 49ers' confidence growing and returning home after spending three of the first four weeks of the 2012 season on the road, it could be a long day for Ryan Fitzpatrick and company.
Let's take a look at what you need to know heading into Sunday's contest.
Where: Candlestick Park, San Francisco, CA
When: Sunday, Oct. 8 at 4:25 p.m. ET
Live Stream: NFL Sunday Ticket
Spread: 49ers -9.5 (per Vegas Insider)
The Bills turned the ball over six times last week against an improved Patriots' defense, but the 49ers are on another level altogether, something that Bills' head coach Chan Gailey is well aware of:
If the Bills come anywhere close to committing the six turnovers that they had last week, the 49ers will simply run the ball down their throats.
Buffalo's defense ranks 28th in the league against the run, having allowed opposing running backs to rush for 548 yards and six touchdowns through four games, an average of 137 yards per game.
Over/Under: 44.5 (via Vegas Insider)
While Ryan Fitzpatrick threw four interceptions last week, he leads the NFL with 12 passing touchdowns and has led the Bills to an average of 28.8 points per game, the sixth-highest average in the league.
Alex Smith and the 49ers aren't far behind the Bills, with their 26 points per game coming in 12th in the league.
Yes, the 49ers' defense is stout allowing only 16.2 points per game, fourth best in the league. But the Bills give up 32.8 points per game (inflated because of last week no doubt), 30th in the NFL.
Bottom line: take the over with confidence.
Key Injuries (via USA Today)
S Jairus Bird (hip), probable
DE Mario Williams (wrist), probable
TE Scott Chandler (head), probable
WR Ruvell Martin (ankle), probable
CB Stephon Gilmore (head), questionable
OG Craig Urbik (ankle), doubtful
WR David Nelson (knee), out for season
TE Mike Caussin (knee), out until late Oct.
DT Torrell Troup (back), out for season
CB Ron Brooks (foot), out until at least Week 6
LB Navorro Bowman (shoulder), probable
CB Carlos Rogers (ankle), probable
RB Brandon Jacobs (knee), probable
DT Issac Sopoaga (knee), questionable
LB Clark Haggans (suspension), out until Week 6
LB Darius Fleming (knee), out for Sunday
LB Parys Haralson (undisclosed), out for season
Key Fantasy Plays
49ers: Frank Gore
As previously noted, the Bills' run defense is, well, awful, and because of that, they can expect to receive a heavy dose of Frank Gore and company early and often.
Consider this: Buffalo allowed the combination of Brandon Boldin and Stevan Ridley to carry the ball 38 times for 243 yards and three touchdowns last week.
Frank Gore, even though he's no longer really a premier fantasy running back, is certainly a better player than either Boldin or Ridley. He should be in for a big day.
Bills: Scott Chandler
If I'm being honest, there isn't one player on the Bills that I would trust to put in my fantasy lineup this week.
But if you have to use someone from Buffalo's squad, consider Chandler.
Yes, he'll be going up against two of the best linebackers around in Patrick Willis and Navarro Bowman, but someone has to catch passes from Ryan Fitzpatrick, and Chandler has become his go-to guy.
He may not find the end zone, but if you play in a PPR league, he'll get you some extra points.
Key to 49ers Win: Mix and Match Coverages
The 49ers are a defensive juggernaut, one that typically doesn't resort to creative schemes and hiding what they are going to do.
They're the kind of defense that walks up to the line, punches the offensive linemen in the mouth as they rush past them to attack the quarterback.
Bills' QB Ryan Fitzpatrick is going to make mistakes, but the 49ers need to get him to make those mistakes early and often. By showing one thing and doing another, Fitzpatrick could easily be lulled into a false sense of security and duped into making a poor throw.
The same goes for blitzes—making Fitzpatrick think the pressure is coming up the middle and sending someone off the edge could easily rattle him and keep him off of his game all day long.
Key to Bills Win: Establish running game
It's easier said than done, especially considering that both of the Bills' best running backs, Fred Jackson and C.J. Spiller, are battling injuries and the 49ers simply don't get run on.
But if they have any chance of pulling the upset, they need to establish a ground game so that Fitzpatrick can run some play-action and give his receivers a chance to get open.
49ers 38, Bills 10
San Francisco's defense is simply too much for an over-matched Bills' offense to deal with. Fitzpatrick will be under pressure all day long and this one figures to be over early.