Exeter manager Paul Tisdale is monitoring the fitness of Jamie Cureton ahead of Tuesday's game.
The striker was substituted 36 minutes into the goalless draw with Swindon at the weekend due to a hamstring injury and is a major doubt for the clash.
Jake Thomson replaced Cureton at the County Ground and is likely to get the nod if the striker fails to be passed fit.
Striker John O'Flynn was recalled to the side at the expense of Richard Logan following impressive substitute and reserve outings in recent weeks and should continue, as should midfielder Ryan Harley, who returned to the side against the Robins' after re-joining the club on loan from Swansea.
Long-serving Grecians' goalkeeper Paul Jones is unavailable for selection after he completed a loan move to Peterborough for the rest of the season.
Southampton captain Dean Hammond could be back in the starting line-up for the game. Hammond has been sidelined for three weeks with a calf problem but is close to returning and will be handed a late check.
Fellow midfielder Adam Lallana is also nearing a return after a knee injury but Tuesday night's trip is expected to come too soon.
Goalkeeper Kelvin Davis and defender Radhi Jaidi were rested against Manchester United in the FA Cup on Saturday and should come back in.
On-loan Leicester winger Dany N'Guessan could make his full debut following a substitute appearance in the 2-1 defeat by the Red Devils.
Striker David Connolly is short of fitness and will not figure while winger Lee Holmes remains a long-term absentee following ankle surgery.