The 28-year-old came off the bench to score twice in the club's 2-1 win away to Crewe Alexandra 10 days ago, earning himself a starting berth tonight.
Clarke, who was reportedly the subject of a £500,000 bid from Wolverhampton Wanderers on Monday, sits out the trip to the capital with a foot injury.
The 28-year-old's absence is manager Steven Pressley's only change from the defeat at the Emirates Stadium.
Leyton Orient: Jakupovic; Omozusi, Clarke, Cuthbert, Baudry; Cox, James, Odubajo, Vincelot; Lisbie, Dagnall
Coventry City: Murphy; Christie, Webster, Seaborne, Adams; Baker, C Thomas, Daniels, Fleck, Moussa; G Thomas