First baseman Mike Napoli was carted off the field with a left knee injury during a Columbus Clippers game on Tuesday night.
Napoli was hurt while attempting to field a popup in foul territory.
"He suffered a significant knee injury," Cleveland Indians manager Terry Francona said Wednesday. Columbus is Cleveland's Triple-A affiliate.
Napoli, who was key in helping the Indians reach the 2016 World Series, signed a minor league deal with the club in February.
The 36-year-old played for the Texas Rangers last season.