Calvin Johnson and rookie Brandon Pettigrew will sit out the team's second consecutive exhibition game, according to head coach Jim Schwartz.
Detroit has a Saturday evening tilt with Cleveland in what has become a traditional "Great Lakes Classic."
Johnson still has swelling in his thumb, and although he's participated in practice, the Lions don't want to risk any unnecessary aggravation of the injury.
Pettigrew will likely miss at least another week of practice with a nagging quadriceps injury.
The team will, however, suit up defensive tackle Grady Jackson for his first exhibition game as a Lion, along with rookie safety Louis Delmas.
Schwartz said the injury situation is improving.
"There were a lot of guys that last week we could have pushed and they probably could have been back if had been November, but it’s August," he said. "We expected to get a lot of those guys back; what we’re hoping is not to get setbacks."
Others that won't participate in the game include place-kicker Jason Hanson (knee), running back Allen Ervin, and receiver Kenny Harris. Tight end Casey FitzSimmons will also remain out.