The visitors will enter the contest off the back of a 2-1 victory over Reading, while Carlisle also triumphed in the league last weekend, overcoming Bolton Wanderers away from home.
Match preview
Carlisle secured a return to the third tier of English football through last season's League Two playoffs, so their main goal for this term is to avoid relegation.
The Cumbrians have won two, drawn five and lost five of their 12 league matches this season to collect 11 points, which has left them in 20th position in the table, three points outside of the relegation zone.
Paul Simpson's side have actually picked up four points from their last two League One fixtures, drawing 1-1 at home to Peterborough United at the start of the month before recording an excellent 3-1 victory away to Bolton last weekend, which would certainly have increased confidence in the camp.
Carlisle were also in action on Tuesday, suffering a 2-0 home defeat to Nottingham Forest Under-21s in the EFL Trophy, but the competition will not take on too much importance for the club this term.
Orient were triumphant in both League Two fixtures between the two sides last season, including a 3-2 victory in the corresponding match at Brunton Park.
The visitors proved to be the best team in League Two last season, winning the title with 91 points, with the club securing a return to League One for the first time since 2015.
A difficult few years has seen Orient play in League Two and the National League, but they are now back in the third tier and will have ambitions of pushing for a top-half finish.
Richie Wellens's side have made an encouraging start to the season, picking up 14 points from their 11 matches courtesy of a record of four wins, two draws and five defeats.
The O's are 16th in the table, six points behind sixth-placed Bolton, and they have won four of their last six matches in all competitions, suffering just one defeat in the process.
Orient suffered a 1-0 loss at Fleetwood Town in their last away fixture at the end of September, but they returned to winning ways on home soil last weekend, overcoming Reading courtesy of a 2-1 scoreline.
Carlisle United League One form:
D
D
L
L
D
W
Carlisle United form (all competitions):
D
L
L
D
W
L
Leyton Orient League One form:
L
W
D
W
L
W
Leyton Orient form (all competitions):
W
D
W
W
L
W
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Team News
Carlisle head coach Simpson made wholesale changes to his side for the EFL Trophy contest with Nottingham Forest Under-21s earlier this week, with youngsters and squad players given opportunities to impress.
There will be a familiar look to the XI for this contest, though, and it might well be the same starting side from the 3-1 success over Bolton in the league last time out.
Jordan Gibson has been in strong form this season, scoring four times in League One, and he is expected to again be joined in the attacking areas by Joe Garner and Sean Maguire.
Orient will be without the services of Max Sanders, who was replaced in the first half of the clash with Reading last weekend after picking up an injury.
Sanders's replacement was George Moncur, who scored the winner in the 90th minute, and the attacker is the obvious choice to be introduced into the XI for this contest.
Head coach Wellens could otherwise select the same side that started last time out, with Joe Pigott, who has netted twice in the league this season, taking to the field as the centre-forward.
Carlisle United possible starting lineup:
Holy; Back, Lavelle, Mellish, Armer; McCalmont, Guy, Moxon; Maguire, Garner, Gibson
Leyton Orient possible starting lineup:
Brynn; Hunt, Cooper, Happe, Turns; Brown, El Mizouni; Moncur, Sotiriou, Archibald; Pigott
We say: Carlisle United 1-2 Leyton Orient
Carlisle have only won one of their last four matches against Orient, and as mentioned, were beaten in both games in League Two last season. We are expecting Saturday's fixture to be close in terms of the general play and scoreline but are backing Orient to navigate their way to all three points.