"He at least has an ACL and probably more," Harbaugh said. "We said a prayer over him, and he'll find a way to come back stronger than before."
Jefferson injured his left knee with a little over nine minutes left in the fourth quarter. He was carted off the field and was eventually ruled out for the remainder of the contest.
The veteran defensive back, who serves as one of the Ravens' leaders on defense, was in charge of relaying the defensive calls to teammates. He entered Sunday's game as the second-leading tackler for the Ravens.
Chuck Clark, who has two starts across three NFL seasons, is expected to replace Jefferson in the starting lineup.
Jefferson's knee ailment is the latest injury to the Ravens' secondary, which already lost nickelback Tavon Young for the season due to a neck injury and has been without cornerback Jimmy Smith for four consecutive contests because of a knee injury.
Through five games this season, Jefferson recorded 21 total tackles and three passes defensed.