Tricolor Paulista are fifth in the table following a 2-0 defeat at Cuiaba, while Vasco currently sit 10th, playing to a 1-1 draw against Juventude the last time out.
Match preview
A series of poor performances in September has prevented Sao Paulo from climbing further up the Brasileiro Serie A standings.
Only one of their previous five matches across all competitions has ended in a victory for them, as they currently sit four points behind Flamengo for fourth and an automatic berth in the Copa Libertadores group stage next season.
Their recent slump has put their hopes of even earning a Libertadores qualifying position in jeopardy, with Soberano only two points above Bahia for one of those spots.
That last league victory came at home against Corinthians (3-1), the 10th this year in Sao Paulo for Luis Zubeldia's men in 15 domestic home contests.
In league play this season, Sao Paulo have failed to win on four occasions when scoring first, dropping 10 points as a result.
The former six-time Brasileiro champions are unbeaten in their last nine home meetings with Vasco across all competitions, claiming a 4-2 victory in this exact fixture last year.
September was also a rough month for Vasco da Gama, as the club was only able to win just one of their five competitive fixtures.
Coming into this midweek affair, they are winless in their last five competitive games, scoring a goal or fewer in each of those matches.
Rafael Paiva's men find themselves just three points above Bragantino, with the latter currently 13th and just outside a place in the next Copa Sudamericana.
Throughout the campaign, the club from Rio have struggled to find the back of the net consistently, going goalless in eight league contests and scoring fewer goals (32) than anyone in the top half of the table.
They have just one victory in their previous six league contests away from home, defeating Vitoria 1-0 at the start of September.
Vasco have not walked away with three points as the visitors against Sao Paulo since beating them 1-0 in a July 2012 top-flight encounter at Morumbi.
Sao Paulo Brasileiro form:
W
L
W
L
W
L
Sao Paulo form (all competitions):
W
D
L
L
W
L
Vasco da Gama Brasileiro form:
W
W
D
L
D
D
Vasco da Gama form (all competitions):
W
D
L
D
L
D
Team News
There are numerous Sao Paulo players dealing with injuries, including Pablo Maia and Alisson, both out for the season with a thigh issue and broken ankle, while Patryck has a sore shoulder.
Ferreira and Moreira are also recovering from thigh issues, Michel Araujo has a knee injury and Welington is suffering from physical discomfort.
Andre Silva and Robert Arboleda both received yellow cards in their match with Cuiaba and will be suspended for this encounter.
Due to an ACL issue, Jair is unlikely to feature for Vasco on Wednesday, while Paulinho and Guilherme Estrella have knee injuries.
Adson is projected to return from his broken leg in late November, David is out for the season after suffering an ACL injury and Souza will be suspended after getting a straight red card in their previous match.
Dimitri Payet had the only goal for Vasco against Juventude, enabling his side to claim a point in what was the Frenchman's first in Serie A this season.
Sao Paulo possible starting lineup:
Rafael; Rafinha, Arboleda, Sabino, Lewis; Liziero, Gustavo; Gomes, Luciano, L. Moura; Calleri
Vasco da Gama possible starting lineup:
Jardim; P. Rodriguez, Victor, Maicon, Piton; H. Moura, Sforza; Coutinho, Payet, E. Rodriguez; Vegetti
We say: Sao Paulo 1-0 Vasco da Gama
Both sides are struggling at the moment, but Sao Paulo seem to recover quicker following a disappointing result, which is why we project them to win a close one.