Cleveland will take on the Minnesota Twins in their 2019 season opener at Target Field on Thursday afternoon.
The team announced Wednesday that Lindor, who was working his way back from a calf injury, suffered an ankle sprain running the bases in a minor league game Sunday.
Lindor was expected to return in about a week, but the latest injury will force him to miss more time.
Ramirez was at the plate in the third inning and fouled a pitch off the inside of his left knee, dropping to the ground in pain.
He was taken off the field a few moments later by a medical cart, and X-rays revealed that he had suffered a contusion.
The two-time All-Star missed the last two exhibition games against the Texas Rangers, but the team remained hopeful he would be able to go in Thursday's opener.
Indians manager Terry Francona said that minus any setbacks Ramirez should be ready to play, and that he took ground balls at the teams' spring training facility in Goodyear, Ariz, on Tuesday.
Last season, in 157 games, Ramirez hit .270 with 39 homers and 105 runs batted in. He's clubbed 68 home runs in the last two seasons for the Indians.