Bills vs. Rams odds: Opening lines for Week 5 matchup

The Buffalo Bills are listed as underdogs for the first time in the 2026 NFL season ahead of their Week 5 Monday Night Football matchup against the Los Angeles Rams. According to FanDuel Sportsbook, Buffalo opens as 2.5-point underdogs on the road. The Rams hold a 2-2 record, while the Bills sit at 3-1 after a Week 4 loss to the New England Patriots.

Both teams face injury concerns heading into the contest. Rams defensive tackle Aaron Donald missed Week 4, while Buffalo deals with injuries to DJ Moore, Ed Oliver, Dee Alford, Te'Cory Couch, Landon Jackson, and Christian Benford. The game marks the first meeting between the franchises since a 44-42 Rams victory in 2024.