Exeter are boosted by the return of experienced forward Marcus Stewart for the trip to Colchester.
Former Ipswich, Sunderland and Yeovil striker Stewart, 37, is back after suspension having missed the Grecians' 4-0 FA Cup win at Southern League side Nuneaton.
Barry Corr and on-loan Charlton striker Stuart Fleetwood led City's attack in that game, with substitute Adam Stansfield introduced for Fleetwood in the second half.
On-loan Tottenham goalkeeper Oscar Jansson has shrugged off a hip injury and will vie with veteran shot-stopper Andy Marriott, who has kept back to back clean sheets, in the absence of injured first choice Paul Jones (knee).
Colchester will be without John-Joe O'Toole.
The on-loan Watford midfielder is suspended after collecting five yellow cards this season.
But boss Aidy Boothroyd can welcome back another central-midfield man in West Ham loanee Josh Payne, who was denied permission to play in the FA Cup last weekend.
Winger Anthony Wordsworth also returns having been suspended for the 4-0 first-round win at Bromley, as does striker Kevin Lisbie who was rested.
Steven Gillespie is pushing for a start after his goal as a substitute.
Centre-halves Paul Reid and Pat Baldwin (both knee) were on the bench after their long lay-offs and could be involved again but winger Ashley Vincent and striker Scott Vernon (both ankle) are still on the sidelines.