Although the Blues dramatically defeated Manchester United by a 4-3 scoreline on Thursday evening, it was a high-intensity contest that inevitably took its toll on the players involved.
With Chelsea also failing to impress in defence, alterations were inevitable, and Pochettino has opted to drop Benoit Badiashile and Mykhaylo Mudryk.
Furthermore, Malo Gusto misses out for the West Londoners, the right-back potentially just being rested given his recent workload.
Trevoh Chalobah will be deployed in the Frenchman's place, Thiago Silva makes his first start in almost two months and Noni Madueke has been included in the final third.
Cole Palmer and Nicolas Jackson join the England Under-21 international in attack, although it is unclear whether Jackson will be deployed down the centre or on the left flank.
Meanwhile, Chris Wilder has made just the two changes to the Sheffield United side that pushed Liverpool on Thursday night.
Ben Osborn has been restored to the team in central midfield, Vinicius Souza being dropped to the substitutes' bench.
Meanwhile, Oliver McBurnie has been preferred to James McAtee in attack, Wilder seemingly sticking with a 3-5-2 and Ben Brereton Diaz being used down the centre.
Cameron Archer is also back in the Blades squad after injury, his first appearance since February.
Sheffield United: Grbic; Holgate, Ahmedhodzic, Robinson; Bogle, Arblaster, Osborn, Hamer, Trusty; Brereton Diaz, McBurnie
Subs: Foderingham, Archer, Norwood, Souza, Slimane, Larouci, McAtee, Brooks, Osula
Chelsea: Petrovic; Chalobah, Disasi, Silva, Cucurella; Caicedo, Fernandez, Gallagher; Madueke, Palmer, Jackson
Subs: Bettinelli, Sharman-Lowe, Gilchrist, Badiashile, Casadei, Chukwuemeka, Sterling, Mudryk, Washington