The Rams currently occupy second place in the League One table, while the visitors head into the weekend in 10th position.
Match preview
After playing out a 2-2 draw with leaders Portsmouth, Derby had to settle for another point in Tuesday's away clash with Wycombe Wanderers.
The Rams were unable to find the breakthrough in a goalless affair, leaving them with a slender two-point advantage over third-placed Bolton Wanderers, who have the advantage of a game in hand.
Following consecutive away matches, Paul Warne's side will now return to Pride Park, where they have won seven of their previous nine home matches, including each of their last four.
Derby have proven to be a tough team to break down in recent home matches, having kept three clean sheets in their last four games at Pride Park.
They may fancy their chances of clinching a fifth straight home win after easing to a 3-0 victory when they met Leyton Orient in December's reverse fixture.
Having collected 62 points from 43 matches, 10th-placed Leyton Orient are on course to secure a top-half finish in their first League One campaign since 2014-15.
Although they can be satisfied with their work this season, the O's would have been disappointed to miss out on a second straight victory in Tuesday's home league clash with Exeter.
Ollie O'Neill and George Moncur gave Leyton Orient a two-goal lead, before Exeter found the net in the 88th minute and the 92nd minute to deny Richie Wellens's side all three points.
After competing in consecutive home games, the O's will now head on their travels for the first away meeting with Derby since August 1981.
The visitors have experienced mixed fortunes in recent road trips, having won and lost three of their previous five away league games.
Derby County League One form:
W
W
L
W
D
D
Leyton Orient League One form:
D
W
L
L
W
D
Team News
Derby are expected to be without the services of Callum Elder, Craig Forsyth, Ryan Nyambe, Jake Rooney, Tyreece John-Jules and Dwight Gayle.
The Rams will have to assess Joe Ward's fitness after he was forced to miss Tuesday's draw with Wycombe due to a knee problem.
Midfielder Max Bird is closing in on a return to action, but it is currently unclear whether he will be ready for Saturday's contest.
Sonny Bradley could be brought into the starting lineup after serving a three-match suspension following his dismissal against Northampton Town last month.
As for the visitors, they are unable to call upon Dan Happe, Theo Archibald, Jordan Graham, Darren Pratley and Idris El Mizouni.
Cyprus international Ruel Sotiriou is also a doubt after he was forced off in the opening 20 minutes of Tuesday's draw with Exeter.
Wellens could be tempted to make a number of changes, with Brandon Cooper, Tom James, Zech Obiero and Moncur all in contention to start Saturday's away fixture.
Derby County possible starting lineup:
Wildsmith; Nelson, Bradley, Cashin; Wilson, Smith, Adams, Sibley; Barkhuizen; Collins, Mendez-Laing
Leyton Orient possible starting lineup:
Bryn; Hunt, Beckles, Cooper, James; Obiero, Brown; Galbraith, Moncur, O'Neill; Pigott
We say: Derby County 2-0 Leyton Orient
While Leyton Orient have little to play for, Derby will be highly motivated to clinch all three points to aid their promotion bid, and we think that they will do enough to continue their impressive home form.