The hosts have only played at St. James' Park twice in their last seven League One games. The division's top scorers will undoubtedly be grateful to be on home turf against the O's on Saturday.
Orient come into the game under new management, after the dismissal of Ross Embleton following the club's 3-1 defeat to Tranmere Rovers.
The Grecians are currently sat in ninth in the league, just two points off of Salford City who occupy the final play-off spot. Leyton Orient also have one eye on the play-offs, but have dropped to 13th due to a poor run of form.
"Jobi was my captain at Reading and is a really good guy. More to the point, he knows football, is really well respected within the game, and I've no doubt the Orient players will want to perform for him. I can see him doing really well."
However, Tom Parkes remains suspended for the hosts, following his red card in the 2-0 defeat to Crawley Town.
Pierce Sweeney is also ruled out for Exeter, with an ankle ligament injury also picked up against Crawley.
Randell Williams is considered a doubt for Matt Taylor's side, but is nearing full fitness again after over two months out with stress-fracture.
Sam Ling's injury is not as bad as first feared; the full-back could miss Saturday's game but may be available for selection sooner than previously expected.
Exeter: Andrésson; Page, Hartridge, McArdle, Key, Taylor, Collins, Jay, Randall, Willmott, Bowman.
Leyton Orient: Vigouroux; Brophy, Happe, Turley, Akinola, Freeman, Cissé, Clay, Wilkinson, Kemp, Abrahams.
Ones to watch
Very rarely is a goalkeeper considered 'one to watch', but Jökull Andrésson's performances have been nothing short of sensational lately.
The Reading loanee originally joined Exeter on a one-week emergency loan but has since seen it extended on multiple occasions. The 19-year-old has started 13 times for the Grecians this season and won the club's player of the month award in February.
Andrésson has become a key figure in the dressing room at Exeter and the youngster's loan in South Devon has certainly kickstarted his career.
Dan Kemp joined Orient on loan from West Ham United in January, after his loan with Blackpool was cut short by the Hammers.
The 22-year-old played his first 90 minutes for Leyton Orient in the victory against Grimsby in midweek, under McAnuff's management. Kemp made a good case for himself, picking up the man of the match award and assisting the winning goal of the game.
Given the chance, the forward will be keen to further impress his new manager against Exeter on the weekend.
The previous two meetings between Exeter and Leyton Orient have both ended as score-draws; earlier this season Jake Taylor rescued a point for the Grecians at The Breyer Group Stadium.
How to watch
The match is available to watch on iFollow through Exeter or Leyton Orient's respective club websites/apps, with match passes available at £10 for those across the United Kingdom.
From 3:00pm, goals and key events will be available to watch as they happen for paying Sky Sports subscribers on Soccer Saturday.