The visitors, meanwhile, would secure their place in the knockout stages with an away win.
Match preview
Having only taken one point from their last three games in this competition, San Lorenzo's place in the Copa Sudamericana is hanging by a thread.
Due to goal difference, Ruben Insua's side need to defeat Palestino by two or more goals on Friday in order to move above them in Group H, which would put them in a commanding position to hold onto second spot given that they host rock-bottom Estudiantes de Merida on the final matchday.
Domestically, San Lorenzo are enjoying a strong campaign, with Insua's side sitting in third position in the first phase of the Argentine Primera Division. However, the fact that they have only won two of their last eight games in all competitions suggests that they have plenty of improvement within them.
While a draw against Palestino would keep their hopes alive, realistically it is a match that they probably need to win if they are to remain in the Copa Sudamericana, which they are hoping to win for the second time in the club's history after triumphing in 2002.
Palestino, meanwhile, are aiming to taste continental success for the first time in the club's history, having finished fourth in the Chilean Primera Division last season.
Founded in 1920 by Santiago's local Palestinian community, Tino have only won their nation's domestic title twice in their entire history - most recently in 1978 - although they did lift the Copa Chile in 2018.
As such, progressing from a Copa Sudamericana group with more illustrious Argentine and Brazilian opponents would represent a major achievement for Vitamina Sánchez's side, who know that two draws from their last two games would be enough to do exactly that.
Given the status of the group, the 50-year-old - who was born in Rosario in Argentina - will be expecting an aggressive performance from his side's forthcoming opponents, but he will have every confidence that they can return from Buenos Aires unscathed.
San Lorenzo Copa Sudamericana form:
W
L
D
L
San Lorenzo form (all competitions):
D
W
W
L
L
D
Palestino Copa Sudamericana form:
W
L
W
D
W
Team News
San Lorenzo appear set to remain without Jeremias James due to a long-term ACL injury, while Jalil Elias is doubtful due to a fever.
Insua may feel forced to rotate given that his side will face Central Cordoba in their domestic division less than four days after this fixture.
Palestino, meanwhile, will travel without Ariel Martinez as the midfielder has ruptured his outer meniscus and will not return until late July at the earliest.
Unlike their opponents, Palestino will have ample rest between this match and their next domestic game against Morning in the Copa Chile on June 22, meaning that Sanchez can name his strongest possible starting XI.
San Lorenzo possible starting lineup:
Batalla; Perez, C Sanchez, Campi; Melli, Perruzzi, Maroni, Braida; Elias, Bareiro; Blandi
Palestino possible starting lineup:
Rigamonti; Ferrera, Meza, Suarez; Cornejo, Vejar, Farias, Carrasc, Munoz; Davila, Barticciotto
We say: San Lorenzo 2-1 Palestino
San Lorenzo will be targeting three points - and ideally a winning margin of at least two goals - so that they head into the final matchday with their destiny in their own hands in terms of remaining in the Copa Sudamericana.
While we think that they should be able to edge to a marginal victory, they may still be relying on a favour from Fortaleza against Palestino on the final day.