Location: Candlestick Park, San Francisco CA
Time: 1:25 PM PT
After spending three of the first four weeks of the season on the road, including a week between games in Youngstown Ohio, the 3-1 San Francisco 49ers are happy to be home. The 49ers play their first of a three game home stand on Sunday. Their opponents, the 2-2 Buffalo Bills, are just happy to be able to play again and get the bad taste from last week out of their mouths. 
It was a tale of two halves’s for Buffalo, who went into halftime leading the New England Patriots 14-7, only to give up six consecutive touchdown drives and lose the game 52-28.  A week later they find themselves on the West Coast, facing what is one of if not the best defense in the NFL.
The Bills will be without two starting offensive linemen, which if true will mean a long day for running backs Fred Jackson and CJ Spiller. One would think if the Bills can’t get their duo in the backfield going, the 49ers defense will start pinning their ears back and coming after the quarterback. Not a environment that Bills quarterback Ryan Fitzpatrick will enjoy operating in. 
The 49ers are good test for the Buffalo Bills defense, which have yet to really prove they can stop an opponents run game. The Bills are 28th in the league in rushing yardage per game allowed, and have given up the sixth most rushing yardage in the league. Last week the 49ers ran for 245 yards and three touchdowns, so it is safe to say a run heavy offense is in game plan for San Francisco. Jim Harbaugh’s favorite. 
That run game will get a big, big boost in former New York Giants running back Brandon Jacobs, who is healthy enough to suit up for the first time this season and make his 49ers debut. It will be interesting to see if Jacobs is used in the jumbo package, for which the 49ers bring in two extra linemen, Leonard Davis and Daniel Kilgore, and play Will Tukuafu, normally a defensive lineman, at fullback. All that beef up front with 6’4 260-pound Brandon Jacobs carrying the football behind them makes for an extremely difficult task for Buffalo.
The 49ers were tough to stop last week because they spread the ball around to so many of their weapons, so look for Offensive Coordinator Greg Roman to do more of the same versus the Bills this Sunday. 
The 49ers vs. Bills matchup is tied 5-5 all time, with San Francisco winning the last matchup in 2008 at home, 10-3.