While their opponents are without a victory in three games, the Uruguayan side earned a share of the spoils with Racing Club in the first fixture of Group E.
Hernan Crespo has some way to go before his managerial record comes anywhere near to what he achieved during his playing days at an array of top clubs.
However, winning the Copa Sudamericana with Defensa y Justicia last year has opened doors for the legendary forward, who was appointed as Sao Paulo boss in February.
Although some games have been against lesser opposition, Crespo already has nine wins from 11 matches, one of those coming against Sporting Cristal in the opening game of Group E.
Sao Paulo have now kept four successive clean sheets, but Crespo knows that his squad can ill-afford any complacency if they want to win their first Copa Liberatores since 2005.
Italian veteran Eder netted one of the three goals against Cristal, his second strike in five appearances since joining the club last month.
Despite their dismal form at the beginning of 2021, Rentistas went agonisingly close to winning the Uruguayan Championship Playoffs, eventually losing out to Nacional in the final earlier this month.
Nevertheless, they were still able to earn a spot in this competition for the first time in their history, even if they started Group E as clear underdogs to progress.
Alejandro Capuccio was naturally disappointed that his team failed to see out the game against Racing Club, eventually recording a draw after conceding a late equaliser.
On a positive note, they perhaps have one more point at this stage than they initially anticipated, giving them some freedom to go on the attack versus their more illustrious hosts.
Sao Paulo will have to make do without Leo after the defender was sent off in the final minute of the meeting with Cristal.
Miranda could be drafted into the team as his replacement, while Eder may get the nod over Pablo after scoring as a substitute last week.
Barring any late fitness issues, Capuccio may stick with the same Rentistas players which produced a strong performance against Racing Club.
However, much will depend on whether Joaquin Sosa is deemed fit after his withdrawal during the second half last week.
Martin Gonzalez is an alternative in the centre of defence if the youngster misses out.
Sao Paulo possible starting lineup:
Volpi; Arboleda, B.Alves, Miranda; D.Alves, Luan, Liziero, Reinaldo; Luciano, Benitez, Eder
Rentistas possible starting lineup:
Rossi; Rodales, Fratta, Gonzalez, Morales; Perez, Cristobal, Duarte, Acosta; Peraza; Rodriguez
We say: Sao Paulo 2-1 Rentistas
Having had over a week to prepare for this contest, Rentistas will fancy their chances of causing the upset.
Nevertheless, Sao Paulo will be motivated to take charge of this group, and we expect the home side to edge to victory by the odd goal in three.