Pato - on loan from Brazilian rivals Corinthians - was ineligible as his parent club easily accounted for Sao Paulo 2-0 last week.
Sao Paulo were played off the park by Corinthians away from home as the hosts made a winning start to their Copa Libertadores campaign thanks to Elias and Jadson.
Muricy Ramalho's men, however, have been boosted by the imminent return of Pato, who bagged a brace in Sao Paulo's 4-0 drubbing of Osasco Audax on Saturday.
Pato has scored six goals domestically for Sao Paulo this season but Ramalho has warned against complacency leading into Wednesday's fixture against the Uruguayan visitors.
"If he plays on the edge, that will bring out the best in him," Ramalho told a press conference.
"He knows that we give everybody a chance. He has come into the team and done well but if he doesn't do well in the next game he will be dropped, otherwise he could become complacent."
Ramalho added: "Together, [Fabiano and Kardec] find it difficult but Pato provides great movement.
"That makes life difficult for opponents and opens up space for team-mates. Pato is an ideal choice to play alongside both of those players. Every time he is on the pitch with one of those two, we score goals."
Group Two rivals Corinthians and San Lorenzo are not in action during the week.
Brazilian Serie A champions and last season's quarter-finalists Cruzeiro kick-off their Group Three campaign in Bolivia on Wednesday.
Cruzeiro, who were eliminated by San Lorenzo last season, take on Club Universitario at Estadio Olimpico Patria.
Copa Argentina winners Huracan and Venezuelan outfit Mineros de Guayana also take to the field for the first time in Group Three on Tuesday, with the two teams meeting in Buenos Aires.
Former Porto and Lyon striker Lisandro Lopez could make his bow for Internacional against Universidad Chile in Group Four on Tuesday after signing a pre-contract.
Internacional will be hoping Lopez faces the Chileans following last week's 3-1 loss to The Strongest.
Emelec and The Strongest go head-to-head in Ecuador on Tuesday.
In Group Five, Boca Juniors host Wanderers on Thursday after both teams won their opening matches.
Zamora and Palestino are in action on the same day.
There is only one match in Group Seven, with Barcelona opening their campaign at home to Estudiantes.
Group Eight leaders Racing Club are at home to Guarani on Tuesday, while Deportivo Tachira travel to Sporting Cristal on Thursday.
Colo Colo and Santa Fe, who were both victorious last week, will clash in Group One on Thursday.
Atletico Mineiro - aiming to bounce back from their 2-0 loss against Colo Colo - entertain Atlas on Wednesday.
