The hosts need to win, and hope results elsewhere go in their favour to stand any chance of finishing in second place, while the visitors have already been mathematically knocked out of the competition.
Match preview
San Lorenzo have collected five points from their opening five group stage games, meaning they are three points behind second-placed Palestino, who host Fortaleza on Tuesday evening.
The Saints need to hope for a three-goal swing of the goal difference if they are to finish in second place, and on paper they are heavy favourites, after winning the reverse fixture 1-0 away in Venezuela.
Despite being withdrawn to 10 men in just the seventh minute of the game, Ruben Insua's side were able to eke out a narrow victory, with Federico Gattoni netting the only goal of the game in the 33rd minute.
Goals have been an issue for San Lorenzo in the Copa Sudamericana, having scored just three times in the competition up to this point, and they have also struggled to find the back of the net in the Argentine Primera Division.
In their last five matches in all competitions, the Saints have scored just one goal, which came in their last match, with Adam Bareiro bagging a second-half equaliser away at Estudiantes.
Estudiantes Merida have also scored just three goals in the Copa Sudamericana up to this point, meaning they have already been eliminated from the competition, however they did show some fighting spirit in their last match in the competition.
The Venezuelan side recorded a shock 1-0 victory against first-placed Fortaleza, with Ervin Zorrilla bagging a second-half winner against the run of play, which should give them confidence heading into Tuesday's game.
That said, Franklin Lucena's side have not been in the best of form in their domestic league, winning just two of their last eight games, meaning they are currently eighth in the table, eight points off the top four.
Last time out, Estudiantes played out a 1-1 draw at home against Carabobo, with Wilfredo Pena cancelling out Francisco Flores' first-half opener with his third goal of the season.
San Lorenzo Copa Sudamericana form:
W
L
D
L
D
San Lorenzo form (all competitions):
L
L
D
D
D
D
Estudiantes Merida Copa Sudamericana form:
W
L
L
L
L
W
Team News
San Lorenzo have been very poor in front of goal recently, so Insua may choose to make a few changes to his side, with Andres Vombergar replacing Nahuel Barrios on the left wing.
After finally bringing his 13-game goalless run to an end last time out, Bareiro is set to lead the line, in what is likely to be a 3-4-2-1 system, with Ivan Leguizamon supporting from the right flank.
As Estudiantes have already been knocked out, Lucena could ring the changes, with David Zalzman replacing Jorge Paez in central midfield, and Gregory Materan coming in for Junior Paredes in attack.
Pena impressed after being brought on as a substitute last time out, and the 22-year-old could be rewarded with a start at left-wing, with Nestor Canelon dropping to the bench.
San Lorenzo possible starting lineup:
Batalla; Perez, Gattoni, Hernandez; Giay, Sanchez, Elias, Campi; Leguizamon, Barrios, Bareiro
Estudiantes Merida possible starting lineup:
Velasquez; Guaramoto, Marquez, Doldan, Martinez; Perez, Zalzman, Canelon, Mercado, Zorrilla; Materan
We say: San Lorenzo 1-0 Estudiantes Merida
Considering Estudiantes Merida have already been eliminated from the competition, they may not be as motivated as their opponents, who still have a chance of qualifying for the next round.
As such, we expect San Lorenzo to eke out a victory, however, given their recent struggles in front of goal, it is unlikely to be a high-scoring game.