El Rojo Paisa will journey to the Estadio Pedro Bidegain looking to snap their run of five consecutive games without a win and turn the tie around following their first-leg defeat.
Match preview
San Lorenzo have enjoyed an impressive 2022-23 campaign as they find themselves in the running for a top-two finish in the Primera Division and have also placed one foot in the quarter-finals of the Copa Sudamericana.
Gonzalo Maroni's 31st-minute strike was enough to hand the Los Santos a 1-0 victory over Belgrano on Sunday and help them established a four-point lead over fourth-placed Lanus in the Argentine top-flight table.
With only two league games left to play, Ruben Dario Insua's men now sit two points behind second-placed Talleres and will be aiming to finish in the top two for the first time since their title triumph in 2016.
San Lorenzo endured an unconvincing run in the Copa Sudamericana group stages as they finished level on eight points with third-placed Palestino and only qualifying on goal difference.
However, they are now on course to reach the quarter-finals for the first time in seven years after grinding out a 1-0 victory over Independiente Medellin in last week's last-16 first-leg clash.
San Lorenzo are currently unbeaten in their last 10 matches, claiming four wins and six draws, and will be backing themselves to finish off an out-of-sorts Independiente Medellin side on Wednesday.
Indeed, Independiente Medellin's form in recent weeks has been nothing to write home about as they have picked up just one win in their last nine outings across all competitions.
Alfredo Arias's men kicked off the new Colombian top-flight campaign on Saturday when they came from behind twice to salvage a 2-2 draw against Deportivo La Equidad at the Estadio Atanasio Girardot.
Felipe Acosta and Luciano Pons scored for either side to end the first half level before Edwuin Cetre converted his 88th-minute penalty cancelled out Francisco Chaverra's 50th-minute strike to force a share of the spoils.
Despite Saturday's resilient team display, Medellin have now gone five straight games without a win, claiming one draw and losing four, including a 3-1 loss to Brazilian outfit Internacional on June 28 which saw them crash out of the Copa Libertadores.
While El Rojo Paisa will head into Wednesday looking to find their feet and turn the tie around, they have struggled for results away from home, where they have lost five of their last six matches since the start of May.
San Lorenzo Copa Sudamericana form:
L
D
L
D
W
W
San Lorenzo form (all competitions):
W
W
D
D
W
W
Independiente Medellin Copa Sudamericana form:
L
Independiente Medellin form (all competitions):
L
W
W
W
L
L
Team News
San Lorenzo remain without experienced striker Ezequiel Cerutti, who has missed each of the last seven matches after suffering a ruptured cruciate ligament back in June.
Siro Rosane picked up a straight red against Belgrano on Sunday but the 23-year-old midfielder is eligible to feature on Wednesday as his suspension applies to only domestic games.
Having rested several key players at the weekend, we expect Insua to name his strongest possible XI on Wednesday, with the trio of Adam Bareiro, Nahuel Barrios and Ivan Leguizamon returning to leading the attack.
Malcom Braida, Jalil Elias, Francisco Peruzzi and Agustin Giay should all be recalled in midfield, while Gaston Campi, Gonzalo Lujan and Rafael Perez should form the defence line shielding Augusto Batalla in goal.
As for Independiente Medellin, Arias will be unable to call upon the services of forward Cetre, who is currently suspended after picking up a straight red in last week's reverse leg.
In has absence, 21-year-old Juan Manuel Cuesta will push for a starting role, teaming up with Junior Barranquilla loanee Brayan Leon Muniz in attack.
Veteran striker Pons was forced off injured at half time against Deportivo La Equidad on Saturday and the 33-year-old is a major doubt for El Rojo Paisa.
Jonathan Marulanda, Jhon Palacios, Victor Moreno and Daniel Londono formed the back four last week and should all start on Wednesday, while David Loaiza and skipper Daniel Torres should retain their roles at the centre of the park.
San Lorenzo possible starting lineup:
Batalla; Campi, Lujan, Perez; Braida, Elias, Peruzzi, Giay; Bareiro, Barrios, Leguizamon
Independiente Medellin possible starting lineup:
Mosquera; Marulanda, Palacios, Moreno, Londono; Torres, Loaiza, Quinones; Monsalve, Cuesta, Muniz
We say: San Lorenzo 1-0 Independiente Medellin
While Independiente Medellin will be looking to overturn their first-leg deficit, they take on a formidable side in San Lorenzo, who have been near impenetrable of late. Buoyed by their home crowd support, we are backing the Argentine outfit to pick up from where they dropped off last week and come out on top once again