Cyprien went down in practice Wednesday while attempting to rush the passer during team drills. Cyprien remained on the ground, holding what appeared to be his left knee. He walked to the sideline on his own after talking to trainers.
"I am devastated to say that he tore his ACL. It's tough for me as a new head coach watching guys work hard in the offseason, play hard and not get a chance to experience the NFL season this year," Vrabel said.
Eighth-year safety Kendrick Lewis is the likely candidate to take Cyprien's spot. Lewis was held out of practice on Thursday because of a minor injury he suffered while making a diving interception on Wednesday.
Vrabel said the Titans will consider other options outside of the organization to replace Cyprien. Kenny Vaccaro and Eric Reid are among the free-agent safeties scheduled to visit the Titans on Friday, sources told ESPN.
Reid has gone unsigned this offseason, and many believe it's because he has knelt during the national anthem the past few seasons to protest racial injustice. He has filed a collusion grievance against the NFL.
Cyprien is in the second year of a four-year, $25 million contract he signed with the Titans in 2017.
He has 499 tackles since entering the NFL in 2013, the most by any defensive back in that span, according to ESPN Stats & Information.
ESPN's Adam Schefter and Mike Triplett contributed to this report.