The Peruvian outfit, on the other hand, will be playing just for pride as they currently sit third in the standings, nine points adrift of the hosts in the qualification spot.
Match preview
Sao Paulo failed to make it two wins from two for the first time in the new Serie A campaign as they were held to a 1-1 draw by Corinthians when the sides squared off last Sunday.
Jonathan Calleri broke the deadlock on the stroke of half time to put the visitors ahead at the Neo Quimica Arena, but substitute Adson found the target with 10 minutes left to play to face a share of the spoils.
Prior to that, the Tricolor Paulista were on a three-game winning streak across all competitions, scoring seven goals and conceding just one since a 1-1 draw at Fortaleza in the Serie A on May 8.
Sao Paulo now turn their attention to the Copa Sudamericana, where they have enjoyed a sensational campaign and already booked their place in the playoffs courtesy of their five-point lead at the top of Group D.
Rogerio Ceni's men head into Wednesday's game on a run of 10 consecutive games without defeat across all competitions, picking up five wins and five draws since a 3-1 loss to Flamengo in the Serie A on April 17.
Ayacucho, on the other hand, were left empty-handed for the third game on the bounce last time out when they suffered a 1-0 defeat at the hands of Melgar.
In a one-sided affair at the Estadio Ciudad de Cumana, 24-year-old forward Luis Iberico came up trumps for the visitors as he broke the deadlock in the 79th minute to hand them a well-deserved victory.
Alejandro Apud's side have now failed to taste victory in each of their last nine games across all competitions, losing seven and picking up two draws, while suffering defeat in four consecutive away outings.
While Ayacucho will look to end this dry spell and bow out of the continental showpiece on a high, next up is a Sao Paulo side who are on an 11-game winning streak on home turf, stretching back to a March's 1-0 loss to Palmeiras.
Sao Paulo Copa Sudamericana form:
Sao Paulo form (all competitions):
Ayacucho Copa Sudamericana form:
Ayacucho form (all competitions):
Team News
Sao Paulo remain without the services of 20-year-old midfielder Gabriel Sara, who has been out of action since last April through an ankle injury.
He is joined on the Tricolor Paulista injury table by fellow midfielder Andres Colorado, who is set to sit out his fifth game on the trot after picking up a muscle problem against Fortaleza on May 8.
Rodrigo Nestor was involved in all three goals in Sao Paulo's 3-0 victory over Jorge Wilstermann in their most recent group outing and the 21-year-old will certainly be one to keep an eye out for.
Meanwhile, Ayacucho will take to the pitch without Francisco Duclos, who sustained a leg injury in the domestic clash with Carlos Mannucci on May 8.
With seven goals and three assists in 12 league outings, Cristian Techera has been in fine form for the Chilean outfit and we expect the 29-year-old forward to lead the attack once again.
Sao Paulo possible starting lineup:
Couto; Rafinha, Miranda, Luizao, Rigoni, Neves, Nestor, Welington; Nikao, Patrick, Eder
Ayacucho possible starting lineup:
Vidal; Magallanes, Salazar, Quina; Chavez, Paucar, Parodi, Guidino; Ardiles, Olascuaga, Techera
We say: Sao Paulo 2-0 Ayacucho
Unbeaten in each of their last 10 outings, Sao Paulo head into this one in solid form and will be looking to close out the group stages on a high. The Brazilian outfit take on an Ayacucho side who have lost four consecutive away games and we predict they will come away with all three points once again.