Paul Smith and Mark Phillips are both struggling to make Southend's home clash.
Goalkeeper Smith was knocked unconscious early on during the club's 1-0 defeat at Gillingham on Tuesday night, and although he fortunately sustained no serious damage scans did confirm a neck injury.
Daniel Bentley replaced Smith at Priestfield and is likely to start against the Grecians, who have not tasted league defeat since the opening day.
Smith's concussion was part of a double injury blow in midweek as centre-back Phillips was forced off at half-time nursing a groin injury having been on the end of a nasty challenge which resulted in a sending-off.
Striker Gavin Tomlin is also battling a niggling groin injury which has hampered him for a while. He will be monitored along with Neil Harris (knee), Luke Prosser (calf), Ryan Leonard (hamstring) and Barry Corr (groin), who have all been sidelined.
Striker Freddy Eastwood finally made his return from a calf injury to make the matchday 18 on Tuesday and he will again hope to be involved.
Exeter boss Paul Tisdale could welcome striker Alan Gow back to his squad.
Gow is now back in full training and is expected to travel, while Guillem Bauza faces a late test to prove his fitness but is unlikely to recover in time.
The Grecians are likely to be without midfielder Liam Sercombe, who missed the midweek victory over Wycombe with an ankle knock.
Tisdale's side did not pick up any fresh injuries during the 3-2 win and the manager is expected to make very few changes as their charge up the table continues.
Exeter are unbeaten in five league matches and sit third in the league.