Buffalo nose tackle Kyle Williams is among five Bills starters who are inactive.
Williams was listed as questionable for the game Friday with a foot problem. Linebacker Shawne Merriman was declared out Saturday with an Achilles tendon problem, joining receiver Donald Jones (ankle), linebacker Chris Kelsay (calf) and tackle Demetrius Bell (shoulder) as inactive.
Jacobs is nursing a mild MCL sprain that caused him to miss Sunday's game against Seattle. His absence means the Giants will rely heavily on Ahmad Bradshaw for the second straight week. Reserve back D.J. Ware also likely will see more snaps.
Bradshaw got a season-high 17 carries last Sunday against Seattle, but amassed just 58 yards. Overall, the Giants rank 28th in rushing yards per game (83.8).
Tuck has missed three of the Giants' first five games this season with groin and neck ailments and is considering sitting out through the team's Week 7 bye.
He did not speak to reporters on Friday but earlier in the week hinted that he was upset over trying to return to the field too early. Tuck played in the Giants' wins over St. Louis and Philadelphia but sat out portions of the Eagles game in Week 3. He has not played since.
"I came back too early, had a setback, and I'm being punished right now," Tuck said on Thursday. "I had sat out the last three weeks like people were telling me to, maybe I'd be playing this week regardless."
Tuck will have to be cleared by doctors before he can return to the field.
As for Snee, he will sit due to a concussion he suffered last week against the Seahawks. Reserve lineman Kevin Boothe likely will replace Snee at guard.
That could change, however, if center David Baas sits Sunday. Baas missed the Seattle game with a burner and is questionable for the Buffalo game, though he expects to play.
If Baas is out, Boothe could start at center, with reserve lineman Mitch Petrus sliding in for Snee.
Long-snapper Zak DeOssie also suffered a concussion against Seattle and the team is calling him questionable for Sunday. He practiced on a limited basis Friday and will have to be cleared by doctors before he takes the field.
"I practiced today and that was a big test," DeOssie said. "So we'll see how it goes but I feel pretty optimistic about it."
Jim Cordle served as the backup long-snapper last Sunday and could take DeOssie's place if he can't go.
Linebacker Michael Boley (knee) and Umenyiora (knee) practiced Friday. Both are expected to play.
Rookie cornerback Prince Amukamara (foot) is out. He has yet to practice since undergoing foot surgery in the first week of training camp.
Ian Begley is a frequent contributor to ESPNNewYork.com. Information from The Associated Press was used in this report.