Castonzo and Leonard suffered rib and groin injuries, respectively, in the Colts' win at Chicago in Week 4. Leonard missed the second half of the game against the Bears due to the injury.
Neither Castonzo or Leonard practiced this week. Reich did not give a timetable on when he expects Leonard and Castonzo to return. After playing at Cleveland, the Colts host Cincinnati in Week 6 before having a bye in Week 7.
Not having Castonzo ends a string of 22 straight starts starts by the Colts' offensive lineman, which includes two playoff games.
"With Myles Garrett and what they do defensively, they move him around," Reich said. "I'm sure he'll switch sides. That's nothing new for him. They'll want to test out Le'Raven. We have our plans on how we'll handle those things. We go into every week with a protection plan no matter who we're playing."
Leonard, the leader of the Colts' defense, has a team-high 27 tackles. The Colts have been the stingiest defense in the league, giving up a league low in yards (236.3) and points (14.0).
Sunday will be the best test of the season defensively for the Colts. Cleveland leads the league in rushing (204.5) and is fourth in points 31.0.