The two sides drew 0-0 in Brazil last week, so the Argentinians will be confident of progressing on home soil.
Match preview
For a club which has generally found themselves sliding on a downwards trajectory in recent years, with three bottom-half finishes in the last four seasons compounded by currently languishing 23rd in Argentina's Primeira Division after 12 games of the second phase, Thursday's quarter-final clash is a humungous one for Estudiantes and their passionate fanbase.
The Rat Stabbers have not reached the last eight of South America's primary continental competition since 2010, which was one year after they last won it in 2009.
Former Manchester United and Chelsea midfielder Juan Sebastian Veron won player of the tournament in that triumphant year after a series of superb performances for his boyhood club, whom he is now chairman of as he looks to help restore the glory years in La Plata.
Ricardo Zielinski, who has been head coach at the club since February 2021, is under immense pressure to progress into the semi-finals given their slide down the league table this season, but the 62-year-old will know not to underestimate their forthcoming opponents despite keeping them at arms length away from home last week.
Indeed, despite having 23 shots and 67% possession across the 90 minutes at Arena da Baixada, Athletico-PR only twice managed to test opposing goalkeeper Mariano Andujar in a somewhat wasteful display.
As is often the case when Brazilian sides meet Argentinian rivals, it was a scrappy affair, with 27 fouls and six yellow cards overall doing little to help the hosts find their rhythm and a crucial breakthrough.
After winning the Copa Sudamericana for the second time last year, former Brazil boss Felipe Scolari is aiming to guide Furacão to a Copa Libertadores triumph for the first time in the club's history.
However, the 73-year-old has a tough job on his hands in terms of helping his side avoid defeat in what is likely to be a ferociously fervent atmosphere against an extremely well-organised opponent.
Estudiantes Copa Libertadores form:
Estudiantes form (all competitions):
Athletico Paranaense Copa Libertadores form:
Athletico Paranaense form (all competitions):
Team News
Estudiantes will be without Fabian Noguera and Ezequiel Munoz, with both defenders some time away from returning from serious knee injuries.
Zielinski made 10 changes for the weekend's 0-0 draw against San Lorenzo, with only central defender Luciano Lollo keeping his place.
With such a tight turnaround between games, the Argentine is likely to significantly shuffle his pack once again, with picking the XI which performed admirably in Brazil last week the likeliest outcome.
Athletico-PR, meanwhile, will travel without former Shakhtar Donetsk winger Marlos due to a calf injury.
Christian Cardoso is also doubtful as he continues his recovery from a knee issue, while Marcelo Cirino is out for a season after suffering an ACL injury.
Like his counterpart, Scolari made 10 changes for Sunday's 3-2 win away to Atletico Mineiro, with only goalkeeper Bento retained in the starting XI.
With an upturn in attacking fluidity, though, Scolari will almost certainly be tempted to make at least a few changes from last week's first leg.
Striker Vitor Roque scored twice in the weekend's impressive league victory and should receive the nod in place of Pablo, while Vitinho may keep his place on the left flank at the expense of Tomas Cuello.
Estudiantes possible starting lineup:
Andujar; Rogel, Lollo, Morel; Godoy, Zuqui, Rodriguez, Mas; Castro, Piatti; Mendez
Athletico Paranaense possible starting lineup:
Bento; Khellven, Henrique, Heleno, Abner; Moura, Fernandinho; Canobbio, Terans, Vitinho; Roque
We say: Estudiantes 0-0 Athletico Paranaense
Estudiantes have drawn each of their last three matches 0-0, and with so much at stake it would not be a surprise if the same outcome occurs on Thursday.
Zielinski's side are incredibly tough to break down and the onus will be on the visitors to break them down without leaving too many gaps at the back.