The hosts have enjoyed a productive start to their second campaign back in the third tier, while the League Two champions are still acclimatising to the rigours of football at this level.
Match preview
Exeter extended their unbeaten run in all competitions to four matches last weekend with a narrow 1-0 victory at the Pirelli Stadium against a Burton Albion side who look set to scrap for survival this term.
The visiting Grecians enjoyed the lion's share of the possession and clear-cut chances in the East Midlands, and all of that pressure paid off in the 75th-minute when midfielder Ryan Trevitt made the net ripple, scoring his second goal since joining on loan from Brentford.
Gary Caldwell's men now return to their Devonshire home for the third time this season, with Exeter sharing the spoils with recently-relegated Blackpool and beating Ruben Selles's Reading at St James Park in August.
A record of 13 points from their opening six games means the Grecians are sitting pretty at the summit of the League One standings, ahead of Bolton Wanderers, Stevenage and Port Vale courtesy of their superior goal difference.
With Sam Nombe, Jevani Brown and Jay Stansfield all moving onto pastures new during the summer, Exeter face a huge task in replacing that trio's attacking threat, however conceding two goals in just six matches will always give you a chance of picking up points.
The Grecians face a busy-looking September schedule, with the high-profile visit of Premier League newcomers Luton Town to come on September 26 in the third round of the EFL Cup.
Cantering to the League Two title last term ahead of Stevenage and Northampton Town, Leyton Orient are finding life in the third tier particularly difficult during the opening stages.
A 2-0 victory over Cambridge United at Brisbane Road at the end of August represents the O's only maximum of the term to date, with Theo Archibald and Shaq Forde getting on the scoresheet against Mark Bonner's men.
Apart from that convincing success on home soil, Orient have struggled to keep their third-tier counterparts at bay so far this term, shipping four goals against Portsmouth, three to Wycombe Wanderers and another three against Steve Evans's recently-promoted Boro.
Similar to Saturday's hosts, the O's have lost a key attacking talent over the summer, seeing last season's 10-goal striker Paul Smyth return to Queens Park Rangers, as the West Londoners hope to avoid relegation from the Championship.
Orient possessed the fourth tier's joint-strongest defence on the road in 2022-23 - conceding just 21 goals in 23 outings - however some of League One's biggest players have already shown that this term will be a different proposition for Richie Wellens's side.
Exeter City League One form:
W
D
L
W
W
W
Exeter City form (all competitions):
D
L
W
W
W
W
Leyton Orient League One form:
L
L
L
D
W
L
Leyton Orient form (all competitions):
L
L
D
W
L
L
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Team News
Exeter have welcomed a new signing to their ranks in the build-up to this weekend's match, with Jack Fitzwater penning at two-year deal at St James Park after leaving Scottish Premiership outfit Livingston at the conclusion of last campaign.
The Grecians' 11th signing of the summer is unlikely to be thrown straight into the starting XI however, with a back three of Pierce Sweeney, Will Aimson and Alex Hartridge expected to line up for the hosts.
Dion Rankine was forced off after 35 minutes of the win at Burton last time out, meaning 22-year-old Vincent Harper could earn his first start of the League One campaign on Saturday.
Viljami Sinisalo is quickly becoming a fans' favourite with his performances since joining on loan from Aston Villa, and the Finland international will be confident of keeping his fifth clean sheet of the season on the weekend.
Leyton Orient have suffered due to a lack of discipline at the beginning of this season, and following dismissals in the EFL Trophy defeat at Gillingham on Tuesday, both Forde and Brandon Cooper are suspended for Saturday's trip to Devon.
Wellens is expected to make a number of changes from the Orient side who were dismantled at Stevenage last weekend, although Cypriot playmaker Ruel Sotiriou should regain his place in the visitors' XI.
Former Birmingham City man Jordan Graham joined the O's in August following his release from the Second City club, and the 28-year-old is relishing game time in his preferred position on the left wing.
Exeter City possible starting lineup:
Sinisalo; Sweeney, Aimson, Hartridge; Niskanen, Trevitt, Carroll, Jules; Harper, Cole, Mitchell
Leyton Orient possible starting lineup:
Brynn; Galbraith; Turns, Happe, James; Moncur, Mizouni, Archibald, Sotiriou, Graham; Pigott
We say: Exeter City 3-1 Leyton Orient
Exeter have been very impressive during the opening stages of the campaign, however those associated with the club believe that Caldwell's side have the ability to improve further - a scary thought for Orient ahead of Saturday's clash.