The hosts have entered the Copa Sudamericana at this stage after finishing third in their Copa Libertadores group, while the visitors just about managed to scrape second in their Copa Sudamericana group.
Match preview
In truth, Medellin were very unlucky to exit the Copa Libertadores, as they were impressive in the group stage, picking up 10 points from six games, which would normally be enough to go through, but they lost their all-important final game against Internacional.
Not only did the Paisa Red lose the crucial encounter against the Brazilian side, they did so in pretty disappointing fashion, going 3-0 down inside the opening 30 minutes, with Luciano Pons's late goal failing to offer them a route back into the game.
Since that defeat at the end of June, the Colombian club have brought in Alfredo Arias a long-term replacement for David Gonzalez, who left by mutual consent in May, with Sebastian Botero overseeing the last 12 games.
Despite an initial uptick in form under the helm of Botero, Medellin have now lost their last three matches in all competitions, meaning there is a great deal of work to be done ahead of the new league season, which begins later this month.
Before the new campaign gets underway, Arias will be looking to get a win on the board in his first home match, but he faces a tough test against a side that do not lose very often.
Indeed, San Lorenzo are sure to be very difficult opponents, given that they have lost just two of their last 16 matches in all competitions, but they have picked up their fair share of draws during that time.
The Saints have shared the spoils in six of their last eight games, but they are unlikely to be disappointed with the result in their last match, in a league fixture against top-of-the-table River Plate.
Ruben Insua's side held the league leaders to a 0-0 draw at the Estadio Pedro Bidegain, in turn keeping themselves in a very strong position to qualify for the Copa Libertadores next season, currently sitting in third place, two points above second-placed Lanus.
To reach this stage of the competition, San Lorenzo have not made things easy for themselves, finishing second in the group by the barest of margins, having conceded one goal fewer than third-placed Palestino.
In their last Copa Sudamericana outing, the Saints recorded a 4-1 victory at home against Estudiantes Merida, ensuring the goal-difference swung back in their favour in dramatic fashion.
Independiente Medellin form (all competitions):
D
L
W
W
W
L
San Lorenzo Copa Sudamericana form:
W
L
D
L
D
W
San Lorenzo form (all competitions):
D
D
W
W
D
D
Team News
Pons is set to lead the line for Independiente Medellin, having impressed in the group stage of the Copa Libertadores, registering five goals and three assists,.
After the disappointing defeat against Internacional last time out, Arias could make a few changes to his new side, as he sets out to implement his own style, with Emerson Batalla potentially replacing Edwuin Cetre at right-wing, having scored two goals in his last four games.
San Lorenzo are struggling going forward, having scored the fewest goals of any side in the top nine of the Argentine Primera Division, finding the back of the net just 22 times in 24 games.
However, another draw would not be the worst result in the first leg of this encounter, so Insua may not choose to make many changes to his side, with Adam Bareiro set to continue at striker, having scored four goals in his last five games.
The manager may be forced into one change in defence, as Carlos Sanchez was withdrawn after just 11 minutes in the last match, indicating he picked up an injury, meaning Gaston Campi could slot into the back three.
Independiente Medellin possible starting lineup:
Mosquera; Monroy, Palacios, Cadavid, Londono; Angulo, Torres, Alvarado, Monsalve, Quinonez; Pons
San Lorenzo possible starting lineup:
Batalla; Lujan, Campi, Hernandez; Giay, Elias, Perruzzi, Braida; Barrios, Leguizamon, Bareiro
We say: Independiente Medellin 0-0 San Lorenzo
Arias will be eager to kick off with a win in his first match in charge of Independiente Medellin, but coming up against one of the best sides in Argentina will not be easy by any means.
Four of San Lorenzo's last eight games have finished as goalless draws, including the last one, and so it would not be a surprise to see a repeat of that result on Wednesday.