Slay has a torn meniscus, an injury that likely will be monitored on a week-to-week basis, a source confirmed to ESPN.
Slay was officially listed as doubtful on the injury report Friday for Detroit's game against the Philadelphia Eagles on Sunday.
The rookie injured the knee during practice Thursday, and Detroit coach Jim Schwartz said Friday it was a "freak" injury that happened during a non-contact practice.
Slay, a second-round draft pick from Mississippi State in 2013, has 27 tackles and four pass breakups this season. He started the first two games of the season for Detroit before being benched for veteran Rashean Mathis.
Slay has become the Lions' third cornerback since, coming in to spell Mathis and Chris Houston when they have been injured. Slay started in place of Houston, who has an injured foot, against Green Bay on Thanksgiving.
Houston is questionable for this week but practiced and would appear to be able to play Sunday against Philadelphia. If Houston and Slay cannot play, look for Bill Bentley and Jonte Green to possibly see snaps in their place opposite Mathis.
ESPN NFL Insiders Adam Schefter and Ed Werder contributed to this report.