Cleveland also put designated hitter Travis Hafner on the 15-day DL with right shoulder inflammation.
With the news, the Indians called up catcher Lou Marson and David Huff from Triple-A Colombus.
Santana's injury could take longer than 15 days to heal and that surgery is an option, yet more will be known later in the week as Santana gets more tests taken and sees a knee specialist, said Soloff.
Santana injured his LCL, which is outside of the knee joint, after he was involved in a violent collision at home plate in the Indians' 6-5 victory over the Red Sox on Monday night at Fenway Park.
"The best-case scenario we wanted him back in three days, but the way he looked, we thought it was going to be much worse, so hearing this is a little bit of relief," said manager Manny Acta.
With one out in the seventh inning, Boston's Ryan Kalish was attempting to score from second base on a single to right field by pinch-hitter Daniel Nava. Shin-Soo Choo threw a strike to home plate, where Santana had his left leg extended to block the dish.
Kalish plowed into Santana's left leg and was tagged out, and both players went sprawling around home plate. While the backstop held onto the ball for the second out of the inning, he immediately fell to the ground in pain.
"Right now, he is in a knee immobilizer that keeps his knee in a comfortable position and is presently on crutches," said Soloff.
The key for doctors and trainers will be figuring out the best way to handle the injury given that Santana is not only a baseball player, but someone who is in as demanding a position as catcher.
The tests results later in the week and Santana's instability over the next two days will allow the Indians to determine what the best treatment options will be.
"All of us feared the worst and you never know what to expect, you fear for potential fractures, ligament injuries inside the knee joint, cartilage issues," Soloff said.
"At this point with the examinations we have undergone, we are not under any of that, so we feel fortunate."
Hafner, who has missed the last five games because of his right shoulder, isn't expected to need more than 15 days to get rid of the fatigue.
As a precaution, Hafner had an MRI taken Tuesday in Cleveland, which doctors and trainers are still evaluating.
"He was still feeling some soreness and if he stayed here, it wouldn't be the most comfortable thing for him and for our ballclub," said Acta.
"Playing every other day or every third day just to lessen the blow would have happened. The fact is, he will now be able to rest and get rid of the fatigue on that shoulder."
Since the soreness Hafner has done rotator cuff strengthening, iced his shoulder and taken anti-inflammatories, yet it still has not proven to be the cure.
When he does return, Acta expects Hafner to be able to play three to four days a week. In the meantime, Acta said Jordan Brown and Shelley Duncan would split time at designated hitter.
"He could have stayed here and been day-to-day," Acta said. "But that wasn't helping him or us."
The shoulder has been a continual problem for the Indians slugger the past three seasons, with Hafner even having arthroscopic surgery in 2008.
"If there is any indication on his prognosis," Soloff said, "it is good as a result of how he has responded over the last five days."
Quinn Roberts is an associate reporter for MLB.com. This story was not subject to the approval of Major League Baseball or its clubs.