The hosts will be aiming to end a four-match winless run as they seek a first-leg advantage on home turf, while the visitors will be hoping to extend their unbeaten streak on the road.
Match preview
Rosario Central are one of eight teams to have dropped down from the Copa Libertadores to South America's second-tier competition.
The Argentine side finished third in their group with seven points and will participate in the Copa Sudamericana for the first time since 2021.
However, Miguel Angel Russo must find a way to halt his side's current four-match winless streak across all competitions, drawing and losing two each, including their last home match against Barracas in the Copa Argentina.
They have also failed to win any of their last three home matches, drawing twice and losing once - furthermore, they have recorded just one victory in their last six matches on home soil.
Meanwhile, Internacional had to settle for the playoff round despite losing only one match during the Copa Sudamericana group stage.
The Brazilian side finished second in Group C with 11 points, one point behind group winners Belgrano, in what was an intense battle for the top spot.
Like their opponents, Colorado are also enduring a six-game winless streak across all competitions, with three defeats and three draws.
However, their away form offers some hope, with three draws and one win from their last four matches on the road - a run Eduardo Coudet will hope his side can extend on Wednesday.
Rosario Central form (all competitions):
W
D
W
L
D
D
Internacional Copa Sudamericana form:
D
D
W
L
W
W
Internacional form (all competitions):
L
D
D
L
L
D
Team News
Argentine midfielder Francis Mac Allister will remain sidelined for this clash, as he is yet to heal from the anterior cruciate ligament injury - which is the same issue that has kept Agustin Bravo out since April.
Abel Hernandez is also unavailable for selection, as he is still currently out with a hamstring injury, while Tomas O'Connor has a hernia and will not be back until later this month.
Agustin Modica scored four goals in as many Copa Libertadores matches, and he is a man to watch on Wednesday.
The visitors will be without several players due to injuries, including Mauricio and Ivan, who are recovering knee issues.
Rene, Lucca, Thiago Maia and Charles Aranguiz are also sidelined with different injuries and will not be available for selection.
Rosario Central possible starting lineup:
Broun; Coronel, Mallo, Komar, F. Rodriguez; Cerrudo, Ibarra, Martinez, Lovera; Copetti, Modica
Internacional possible starting lineup:
Anthoni; Bustos, Vitao, Fernando, Renan; Henrique, Romulo, Gomes, Wesley; Patrick, Valencia
We say: Rosario Central 1-1 Internacional
Enjoying a four-match unbeaten run on the road, Internacional should be confident of securing a positive result here to put them in a good position ahead of the second leg.