McCoy, 27, sustained a hamstring injury during training camp in August and has not been completely healthy since.
A three-time Pro Bowl selection, McCoy is in his first season with the Bills after being traded by the Philadelphia Eagles in the off-season for linebacker Kiko Alonso.
In three games this season, McCoy has 146 rushing yards, 83 receiving yards and one touchdown.
Rookie running back Karlos Williams has led Buffalo's rushing attack in 2015, as he is the league's current leader in yards per rush with 7.8 per carry. On 24 carries this season, the fifth-round selection has tallied 186 yards and three touchdowns.
ESPN's Adam Schefter reports that with Williams playing well, Buffalo could decide to rest McCoy until his hamstring is healthy.
The Bills (2–1) host the Giants (1–2) on Sunday at 1 p.m. ET on FOX.
- Kayla Lombardo