Mccoy is dealing with a hamstring injury that he suffered early in Buffalo's loss last week to the New York Jets.
McCoy is averaging a career-low 3.3 yards per carry through 12 games and has only found the end zone twice this season.
If McCoy and Ivory cannot go, Buffalo's backfield will consist of Marcus Murphy and Keith Ford.
Ford, an undrafted free agent from Texas A&M, was promoted from the team's practice squad earlier this week.
LeSean McCoy and Chris Ivory aren't locks to be on the Bills' roster in 2019 and Murphy will be 28 in 2019.
A strong performance on Sunday versus the Lions could lead to Ford getting more opportunities over Buffalo's final two games against the New England Patriots and Miami Dolphins.
- Five things to watch: Lions vs. BillsThe Detroit News
- Detroit Lions vs. Buffalo Bills: Live game blog, score updatesDetroit Free Press (blog)
- How to watch Lions vs. Bill: Start time, TV channel, streamMLive.com
- Little to play for in Lions/BillsOlean Times Herald
- Detroit Lions' Romeo Okwara makes the most of chance as Ansah fill-inDetroit Free Press
- Buffalo Bills vs. Detroit Lions: Three keys to a Bills victoryBuffaloLowDown
- Bills RB LeSean McCoy not expected to play against LionsLarry Brown Sports
- Bills wary of Stafford despite drop in productionThe Oakland Press
- Injuries: Bills' McCoy (hamstring) a game-time decisionNFL.com