Despite their superiority before the gameweek 17 fixture, Tricolor Paulista cannot go into the encounter expecting not to have to earn maximum points against last season's second-placed team.
Match preview
Sao Paulo are back to action six days after a surprising defeat at the hands of Atletico Mineiro, who had lost two on the trot and were winless in three before gameweek 16.
The defeat put paid to the club's four-match winning streak that followed a four-game sequence without a victory (two draws, two losses).
Luis Zubeldia will hope to avoid another such run of winless games, giving the hosts the necessary motivation to get back to winning against inferior opposition, going by this campaign's results.
With three wins on the trot and five triumphs in total at Estadio Cicero Pompeu de Toledo, a fourth straight home success seems the likely outcome.
Five of their last six in front of their supporters have been victories, with Cuiaba denying them in a 1-0 shock result at the backend of June after playing out of their skins in Morumbi.
It remains to be seen if Gremio are fortunate enough to avoid losing to one of the form sides in the competition, especially as their relegation form and road results inspire little confidence.
Clube de Todos have notched three wins in 14 games this term — only three sides have more — and their nine losses are one fewer defeat than cellar-dwelling Fluminense.
Things look extra bleak for Renato Gaucho's men on the road, underscored by picking one point away from Porto Alegre, joint-worst with the league's bottom club.
The travelling contingent hope for a positive outcome on their seventh away try this term, keen to get points on board to avoid being left behind in the relegation battle.
Nevertheless, two outstanding games mean the visiting club's situation is not totally dire, as they are four points from safety with 16th-placed Vitoria on 15 points.
Sao Paulo Brasileiro form:
L
W
W
W
W
L
Gremio Brasileiro form:
L
D
W
D
L
L
Gremio form (all competitions):
D
W
D
L
L
W
Team News
Zubeldia's team will have to make do without the suspended pair of Alan Franco and Luiz Gustavo, while Colombia's James Rodriguez, named the best player at the concluded Copa America, is not expected to return to club action so quickly.
Juan and Giuliano Galoppo have foot injuries that could rule them out of Wednesday's game and Joao Moreira and Pablo Maia are not anticipated to feature because of thigh issues.
Walter Kannemann is suspended for Gremio after his sending-off in the 2-0 home defeat at the hands of Cruzeiro and former Atletico Madrid and Chelsea striker Diego Costa misses out because of a muscle injury.
Also absent for the away team are Andre Henrique (ankle), Lucas Milla and Jhonata Robert (both have knee issues).
Everton Galdino was among the goalscorers in a rare victory against Operario PR in the domestic cup, and the forward hopes to keep that run going against the in-form club.
Sao Paulo possible starting lineup:
Rafael; Vinicius, Arboleda, Ferraresi, Welington; Moura, Alisson, Bobadilla, Ferreira; Luciano, Calleri
Gremio possible starting lineup:
Marchesin; Pedro, Geromel, Jemerson, Silva; Edenilson, Pepe, Villasanti; Pavon, Galdino, Soteldo
We say: Sao Paulo 2-0 Gremio
After going winless in both games on their turf to start the season, picking one point from six, Sao Paulo have secured 15 points from the next 18 to boost their prospects of at least ending higher than last season's 11th.
They should defeat a team that have scored just three times and secured one road point from six matches.