The hosts, meanwhile, will be looking to return to winning ways after experiencing a six-game winless run in all competitions.
Match preview
Since beating Carlisle United in November's FA Cup tie, Leyton Orient have gone on to draw two and lose four of their next four matches.
After drawing with Wigan Athletic and Bristol Rovers in their last two league games, the O's fell to a disappointing 1-0 defeat in last weekend's second-round FA Cup tie against fifth-tier Chesterfield.
While the O's have now gone over a month without a competitive victory, their wait for a league win stretches back to October 14.
With wins proving to be hard to come by in recent times, Richie Wellens's side head into the weekend in 16th place with 22 points to their name and six points separating them from the bottom four.
Having lost all four home league games where they conceded first, Leyton Orient may need to net the opening goal if they are to trouble Derby on Saturday.
Derby carry significant momentum into the weekend after recording four consecutive league wins, including a narrow 1-0 victory in last Saturday's away clash with Port Vale.
Tyreece John-Jules scored the decisive goal in the 77th minute to ensure his side finished the last round of the fixture in sixth place and two points clear of the chasing pack.
The Rams enjoyed more success in Tuesday's EFL Trophy fixture against Fleetwood Town, with James Collins netting a brace before John-Jules found the net for a second straight game to wrap up a comfortable 3-0 home win and secure Derby's place in the last 16.
They will now turn their attention back to Saturday's contest, where they will be looking to continue their solid defensive record, having kept four clean sheets in their last six league matches.
As a result of their resolute backline, the Rams have conceded just 16 league goals this season, leaving them with the joint-best defensive record alongside leaders Portsmouth.
Leyton Orient League One form:
D
D
L
L
D
D
Leyton Orient form (all competitions):
L
L
L
D
D
L
Derby County League One form:
W
L
W
W
W
W
Derby County form (all competitions):
W
W
L
W
W
W
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Team News
Leyton Orient forward Aaron Drinan is set to miss six to eight weeks of action after picking up an injury against Bristol Rovers at the end of November.
After dropping down to the bench last weekend, defender Dan Happe may be recalled to the lineup for Saturday's home fixture.
Forward Joe Pigott could also come back into the side after settling for substitute appearances in Leyton Orient's last two matches.
As for Derby, they are unable to call upon the injured trio of Conor Washington, Liam Thompson and Jake Rooney.
Korey Smith is also a fitness concern after missing the last two matches, while Ryan Nyambe and Martyn Waghorn are doubts due to groin and calf issues respectively.
After netting a brace in Tuesday's EFL Trophy victory, Collins will now look to add to his seven-goal league tally when he leads the line against Exeter.
Leyton Orient possible starting lineup:
Brynn; Cooper, Happe, Turns; James, Brown, El Mizouni, Archibald; Sotiriou, Pigott, Forde
Derby County possible starting lineup:
Wildsmith, Wilson, Nelson, Cashin, Forsyth; Fornah, Bird, Hourihane; Ward, Mendez-Laing; Collins