In the opening leg last week, the Chileans failed to take advantage of their lengthy possession (71%), conceding four goals in just over an hour of play.
Match preview
It has been a decade since Sao Paulo clutched this South American trophy, and based on their form after seven matches, they seem like the odds-on favourite to reclaim the title in 2022.
10 years ago, legendary goalkeeper Rogerio Ceni played a big part in their triumph at the Copa Sudamericana, conceding only twice in their eight games played en route to the championship.
Now the manager of this team, Ceni has turned the current generation of Sao Paulo players into a potent attacking unit, scoring the fourth-most times (20) domestically this season, while notching multiple goals in five of their seven fixtures at this season's tournament.
Throughout the competition, Tricolor Paulista have trailed for all of three minutes, while never being behind heading into half-time.
In 11 previous meetings against clubs from Chile at this competition, Sao Paulo have never lost, conceding only once at home over that span, to La Catolica back in 2013.
Heading into the second leg down by a pair of goals seems like a steep hill to climb for the record 16-time champions of Chile.
Their history in this competition would back that thought, as UC have not gone on to win a knockout round when facing a deficit heading into the deciding leg since 2005, trailing 2-1 after their opening game that year, before defeating Fluminense 2-0 in the return fixture, advancing to the semi-finals.
Manager Ariel Holan can look to his team's domestic campaign as evidence that their current predicament could be reversed, when they scored three unanswered goals in February, defeating Coquimbo 3-2.
If they can strike first on Thursday, Catolica might be in with a fighting chance, having won their last six games in which they tallied the opener, while scoring multiple goals in four consecutive encounters in all competitions.
Universidad have an aggressive group who win their share of duels in the middle of the field, while usually with the bulk of the possession, which they will need to continue on Thursday in their quest to advance.
Sao Paulo Copa Sudamericana form:
Sao Paulo form (all competitions):
Universidad Catolica Copa Sudamericana form:
Universidad Catolica form (all competitions):
Team News
A brace from Luciano helped lead Sao Paulo to victory in the opening match versus La Catolica, while Reinaldo and Jonathan Calleri both tallied a goal and an assist and Igor Gomes had one assist himself.
Tricolor Paulista will have three players suspended for this deciding fixture as Calleri, Rodrigo Nestor and Igor Vinicius were all shown red cards in Santiago.
Ceni has several players currently struggling with their fitness as Caio (ACL) is done for the season, while Talles Costa (ankle), Rafinha (flu), Robert Arboleda (broken ankle) and Luan could all be sidelined with injuries.
Unfortunately, it does not end there for Sao Paulo, with Alisson out due to a sprained knee. Andres Colorado might be recovered from his thigh issue, but Nikao and Gabriel Sara are not expected back until the middle of July with ankle injuries.
Goals from Fernando Zampedri and Diego Valencia were not nearly enough for Catolica in the first match at home to Sao Paulo, where captain Jose Pedro Fuenzalida and Gonzalo Tapia collected assists.
Zampedri notched a brace over the weekend as UC blanked Coquimbo 2-0, with Cristian Cuevas assisting on his second goal, while Matias Dituro only had to make two saves to preserve the clean sheet.
The Chileans only tallied five times in the group stage of the Libertadores, with Zampedri scoring twice, while Marcelino Nunez, Mauricio Isla and current Flamengo defender Pablo all found the back of the net once.
Over the weekend, Holan inserted four new players into the opening lineup, as Dituro replaced Sebastian Perez in goal, while Branco Ampuero, Felipe Gutierrez and Diego Valencia started in place of Tomas Asta-Buruaga, Luciano Aued and Cristian Cuevas.
Sao Paulo possible starting lineup:
Jandrei; Leo, Miranda, Costa; Neves; Patrick, Gomes, Reinaldo, Anderson; Luciano, Rigoni
Universidad Catolica possible starting lineup:
Perez; Isla, Ampuero, Asta-Buruaga, Cuevas; Saavedra; Fuenzalida, Nunez, Gutierrez, Orellana; Zampedri
We say: Sao Paulo 2-1 Universidad Catolica
With the deficit they are facing, Universidad have no choice but to take chances to try to claw their way back into this tie.
That should allow Sao Paulo to do what they did in the opener, catch the Chileans on the break, a tactic they executed to near perfection last Thursday.