Luplow has been dealing with an ankle issue since training camp, and continued soreness and swelling over the past few days forced the Indians to make the move Friday before opening a three-game series against the Toronto Blue Jays.
Indians manager Terry Francona said Luplow underwent an MRI to evaluate the injury.
"We're trying to figure it out," Francona said. "I think it's in a little different area or examining different from spring training. We're trying to, obviously, find out what's going on there. Ultimately what matters is if something's bothering the player and he can't play like he wants, you can call it anything you want, but we need to find out. So that's what we're doing."
To take Luplow's roster spot, the Indians recalled right-hander Eli Morgan, who will make his major league debut by starting the series opener against the Blue Jays.
Luplow is batting .165 with seven homers and 20 RBIs in 36 games.