Sunday will mark the sixth meeting between the Bills and Ravens, who lead the series 3-2.
Baltimore picked up a 37-34 overtime victory in the most recent encounter on Oct. 24, 2010 at home.
The Bills have won the only previous meeting in Buffalo, a 19-14 triumph on Oct. 21, 2007.
WHAT TO WATCH FOR
Ravens running back Ray Rice (hip) missed a game for the first time since his 2008 rookie season when he did not suit up against the Texans, though Harbaugh said on Monday that both he and defensive end Chris Canty (thigh) were close to playing.
Minus Rice, Bernard Pierce ran for 65 yards on 24 carries with a score. He will likely continue to get work even if Rice can play this weekend, but it should be quarterback Joe Flacco who has the big game versus the Bills.
Buffalo's secondary is besieged by injuries right now to all three of its top corners. Stephon Gilmore and Ron Brooks are sidelined due to wrist and foot issues, respectively, while Leodis McKelvin suffered a leg injury in the first quarter versus the Jets.
Minus McKelvin, head coach Doug Marrone moved Aaron Williams from free safety to corner with Jim Leonhard shifting to his spot.
The Jets took full advantage, logging four plays of 40 yards or more, including TD passes of 51 and 69 yards that saw third-year man Justin Rogers burnt on both plays.
Marrone didn't single Rogers out after the game, saying it was the whole secondary that struggled.
"Everybody's going after our secondary and we just have to do a good job," said the Bills coach. "We're trying to change things up for them coverage-wise and pressure and do that to try to keep the quarterback thinking. But hey, when they bring the pressure, block them all up. They went one-on-one and it's just a point of we didn't make those plays."
Said Rogers of moving on from the performance, "Yeah, I think I've been able to for the most part. You know it was unfortunate and I was hard on myself but the thing about this game is you have to move on."
Overall, the Bills rank 28th in total defense at 417.3 yards allowed per game.
Should McKelvin be unable to suit up, Ravens long threat Torrey Smith could have a monster day. He is averaging 16.8 yards per reception.
Flacco threw for 250 yards with three touchdown passes and no interceptions for a 111 passer rating in his only previous meeting with the Bills. He could be thin behind him at running back after Pierce's backup, Shaun Draughn, suffered a high ankle sprain versus the Texans.
"It will be there. We can't force anything," Flacco said of the long ball. "We still have to take chances. It's not like they're high percentage all the time. They're either going to be completed, and it's going to be a big play, and that's the risk you take. If not, you're sitting there at 2nd-and-10 or whatever it may be. I think, overall, we just have to click a little bit more on everything we're doing."
Also for Baltimore, backup nose tackle Terrence Cody sustained a sprained knee last weekend and Harbaugh said it would be a stretch to get him back for this game.
After getting sacked eight time last weekend, Manual may be in for another long day against an improving Ravens defense. Linebacker Terrell Suggs is looking to record a sack for a fourth straight game and has four in four career meetings with the Bills.
Smith, meanwhile, leads the club with 25 tackles to go along with 1 1/2 sacks.
"Daryl has just done a great job, and for him to come up (with big plays), it's not just the interception. He's played really well consistently from the beginning," Harbaugh said of his linebacker.
The Bills defense is being led by Mario Williams' 4 1/2 sacks and 27 tackles by Kiko Alonso, who is just the second rookie linebacker in team history to record an interception in back-to-back games.
Buffalo running back C.J. Spiller had nine yards on 10 carries versus the Jets before suffering a thigh injury, but expects to play this weekend.
"It's sore, but it shouldn't be anything that will keep me out this week," Spiller said on Monday. "I should be feeling better day-by-day. Just taking it slow, just a little sore right now."
The Bills do have a capable backup in Fred Jackson, who ran for 72 yards on seven carries last weekend, though 59 came on one play.
The Ravens seemed lost in the woods following a Week 1 loss and slow start the following weekend versus Cleveland, but have survived thus far because of their defense.
Baltimore needs more out of the highly-paid Flacco and should get it this weekend against an injury-ravaged Bills secondary despite the lack of playmakers in the receiving game, a unit complicated by an injured Rice. His return will allow Flacco to look deep towards Smith and Marlon Brown while having Rice to check down to.
Buffalo has managed to be in each game it has played so far, but will get all it can handle against a confident Ravens defense.
Sports Network Predicted Outcome: Ravens 27, Bills 17