Sao Paulo won the first leg 1-0 a week ago on home soil, but have struggled greatly on the road all season.
Match preview
With a place in the semi-finals up for grabs, Palmeiras will be eyeing up a comeback to keep alive hopes of a fifth Copa title, with their last coming in 2020.
It is a much different story for Sao Paulo though, as they are yet to taste success in this competition, with reaching the final in 2000 the best they have achieved.
The two sides met in the cup last season in very similar circumstances with Sao Paulo leading 1-0 from a home first leg, and they would go on to progress from the last 16 via a penalty shootout after Palmeiras won 2-1 in normal time.
Palmeiras need to put up a much better performance than they did in the first leg if they are to have any chance of turning the tide in the tie though.
Abel Ferreira's side managed only one shot on target in defeat, registering an xG of just 0.18.
Further disappointment at the weekend means Palmeiras are winless in five domestic matches, after Giorgian De Arrascaeta's late strike earned Flamengo a point at Allianz Parque in a game which was overshadowed by crowd trouble which turned fatal.
A woman in her 20s was pronounced dead after being struck by a glass bottle as ugly scenes ensued before the match at the weekend, with nationwide condemnation coming the way of both sets of supporters.
The result means that Palmeiras have collected just two points from a possible 12, resulting in them dropping out of the Brasileiro top four.
Lying down in fifth, the side now find themselves a huge 12 points behind league leaders Botafogo.
The last domestic encounter Palmeiras won came against Sao Paulo early last month in the league, but even then that might not be enough, as was proved in last season's cup clash.
Sao Paulo's away form this season will give the hosts hope though, as they have won just four points from seven away league games this season - the second-worst in the Brazilian top flight.
Dorival Junior's men capitalised on their strong home form to take the lead in the tie in the first leg though, making it 10 wins from 12 at home.
A repeat of their 0-0 draw with Bragantino at the weekend will be much welcome, and that is the exact scoreline that the last two meetings between the sides have ended at Allianz Parque.
Palmeiras Copa do Brasil form:
Palmeiras form (all competitions):
L
L
W
D
L
D
Sao Paulo Copa do Brasil form:
Sao Paulo form (all competitions):
W
L
W
W
W
D
Team News
Rafael Navarro was not in the Palmeiras squad at the weekend, and the attacker has since completed a loan move to MLS side Colorado Rapids.
Midfielder Ze Rafael and Colombian Eduard Atuesta were also absent with injury and are set to remain the only absentees for the hosts.
Artur returned after two games out to start against Flamengo and could keep 16-year-old Endrick out of the side, after he started in the first leg.
After scoring the winning goal in the first leg, Sao Paulo's veteran full-back Rafinha missed the weekend draw with Bragantino.
The 37-year-old joined a long list of injury absentees, who are all expected to miss out again here.
Giuliano Galoppo and Talles Costa are out in midfield, while defenders Igor Vinicius and Welington join Erison on the sidelines.
Palmeiras possible starting lineup:
Weverton; Mayke, Gomez, Murilo, Piquerez; Richard Rios, Luan, Gabriel Menino, Raphael Veiga; Dudu, Artur
Sao Paulo possible starting lineup:
Rafael; Nathan Mendes, Arboleda, Franco, Caio Paulista; Pablo Maia, Gabriel Neves, Luciano; Wellington Rato, Calleri, Rodrigo Nestor
We say: Palmeiras 1-0 Sao Paulo
Form often goes out of the window in tense derby matches, but with neither side showing much of late, this game could go the distance.