Both are close to confirming safety after improving their form, but the hosts will want to avoid being surpassed by their visitors from the capital.
Match preview
Overcoming a red card for Zak Jules just before half time, Exeter saw out a 1-0 home victory over Burton Albion earlier this month, both extending their unbeaten run to three matches and continuing a climb up the League One table.
Since Reece Cole's strike secured maximum points at St James Park, the Devon club have been back in training, as last Saturday's game against Leyton Orient was postponed due to the international break.
Almost a fortnight after City were last in action, they will aim to continue their move away from the bottom four, and Gary Caldwell's side are also seeking three league wins in a row for the first time since September.
Having extended their lead over the drop zone to 11 points, Exeter have all but maintained third-tier status for another season, but Caldwell cannot be entirely happy with their results on home turf this season.
The Grecians have won only six of 20 fixtures as hosts, while averaging well under a goal per game, as their longstanding struggles in the final third have continued.
By contrast, Friday's visitors have scored freely in recent games between the two clubs: Charlton ran out 4-1 winners at The Valley in October, when Alfie May bagged a brace, and have found the net at least twice in four of the last five meetings.
In fact, Charlton have won each of their last five league matches against Exeter, including both of their last two visits to St James Park: the London club had previously managed just one victory in the previous 13, so the tide seems to be turning in their favour.
Rejuvenated under Nathan Jones, the Addicks drew 1-1 with Fleetwood Town last time out, to extend their unbeaten streak to eight games - only conceding a late equaliser denied them maximum points at Highbury Stadium.
Sitting 16th in League One, on 45 points, Charlton are within touching distance of rubber-stamping their place in England's third tier for next term, with May scoring crucial goals on a regular basis.
While Jones lost his first game in charge, he has not tasted defeat in the league since, and his new side are some nine points clear of the relegation places.
Having earned 19 points from 60 available away from home - courtesy of three wins and 10 draws - Charlton are now looking to prolong a five-match unbeaten streak on the road; another win would take them above Exeter in the standings.
Exeter City League One form:
L
D
L
D
W
W
Charlton Athletic League One form:
D
W
D
W
W
D
Team News
Gary Caldwell has now welcomed back five players who were away on international duty while Exeter were training this week, as Finland duo Ilmari Niskanen and Viljami Sinisalo, Wales Under-21 midfielder Luke Harris, Suriname's Yanic Wildschut and Sudan star Mo Eisa all returned to the fold.
Zimbabwe striker Admiral Muskwe has been out injured for some time now, alongside winger Demetri Mitchell, while Zak Jules must serve a suspension due to his dismissal against Burton.
Cheick Diabate may therefore come into the hosts' back three, which should also feature mainstays Pierce Sweeney and Will Aimson.
Meanwhile, Charlton are still without highly-rated Miles Leaburn due to a serious hamstring injury, so Daniel Kanu is set to support Alfie May up front.
The latter is League One's leading scorer, on 21 goals, and will lead the line in a likely 3-5-2 formation.
Exeter City possible starting lineup:
Sinisalo; Sweeney, Aimson, Diabate; Niskanen, Woods, Cole, Wildschut; Aitchison, Harris; Cox
Charlton Athletic possible starting lineup:
Isted; Edmonds-Green, Thomas, Gillesphey; Watson, Anderson, Coventry, Dobson, Small; Kanu, May