The Argentine outfit will be looking to capitalise on home advantage as they bid to establish a first-leg lead ahead of the return fixture.
Match preview
Currently 24th in the Primera Division after playing nine matches, San Lorenzo will return to Copa Libertadores action after progressing to the knockout stages as Group F runners-up.
The Argentine side will aim to exploit home support as they seek to secure a place in the next round, hoping to lift the continental trophy for the second time following their 2014 triumph.
However, Los Santos are in poor form heading into this clash, having failed to win any of their last four matches across all competitions.
Since defeating Gimnasia on July 23, Leandro Romagnoli's side have drawn consecutive games with Newell's Old Boys and Independiente in the league, before suffering back-to-back defeats - a 3-1 loss to Velez Sarsfield in the Copa Argentina Round of 16 and a 1-0 defeat against Atletico Tucuman in their most recent league match.
Wednesday's encounter will be the third meeting between the two sides, having faced each other in the Copa Sudamericana in 2018, with Los Santos claiming a home win before a goalless draw in the second leg.
In the current Copa Libertadores campaign, the hosts are unbeaten at home, recording two wins and one draw in three matches, and they will hope to maintain this record in the round of 16.
Meanwhile, Group G winners Atletico Mineiro enter this clash looking to build on their solid group stage form, where they won five and lost just one of their six matches.
Galo, who lifted the trophy once in their history in 2013 - a year before the hosts' triumph - will be aiming to go all the way again.
They head into this match on a two-game unbeaten streak - a 3-0 win over CRB in the second leg of their Copa do Brasil Round of 16 tie followed by a goalless draw with Cruzeiro in their most recent league match.
With two victories and a defeat in their three away matches during the Copa Libertadores group stage, the visitors will be looking to replicate one of those wins on Wednesday.
However, they are without a win in their last five away games across all competitions, recording three draws and two defeats since a 1-0 victory over Internacional on June 27 in the Brazilian Serie A.
San Lorenzo Copa Libertadores form:
D
L
L
W
W
D
San Lorenzo form (all competitions):
L
D
W
D
D
L
Atletico Mineiro Copa Libertadores form:
W
W
W
W
L
W
Atletico Mineiro form (all competitions):
W
W
D
L
W
D
Team News
San Lorenzo will be without long-term absentees Manuel Insaurralde and Gaston Hernandez, who are both sidelined with cruciate ligament injuries.
Midfielders Malcolm Braida and Eric Remedi are also out injured until later this month, while Braida is recovering from a knee injury, Remedi is nursing a strain.
Atletico Mineiro will be missing their leading Serie A scorer this season, Hulk, who is out with calf strain, while Alisson is also sidelined with a sprained ankle.
Mauricio Lemos is doubtful with a muscle injury, and Eduardo Vargas is recovering from a knee problem.
San Lorenzo possible starting lineup:
Altamirano; Arias, Romana, Campi, Baez; Tripichio, Irala; Reali, Barrios, Leguizamon; Cuello
Atletico Mineiro possible starting lineup:
Everson; Saravia, Battaglia, Alonso, Arana; Otavio, Vera, Franco, Scarpa; Paulinho, Cadu