Despite a poor start to the league campaign, the hosts impressed to advance in second place, while their visitors topped their group with 12 points.
Match preview
After sneaking into fourth place in the Campeonato Brasileiro Serie A table on the final day of last season, Fortaleza earned automatic entry into the Copa Libertadores group stage, but they had to endure a tough start.
Defeats to Colo Colo and River Plate left them without a point from the opening two rounds of fixtures, before the Leao do Pici were able to bounce back with a 2-1 win over Alianza Lima.
A draw with River Plate kept them in the fight for qualification heading into the final two games, and they went into second spot by completing a double over the Peruvian side.
That left Juan Pablo Vojvoda's side leading Colo Colo on goal difference heading into their crucial final-day contest in Chile, and they eventually prevailed with a 4-3 win to book their place in the final 16, as Moises hit a brace alongside goals from Silvio Romero and Yago Pikachu.
While their continental form has been a shining light, Fortaleza have displayed concerning form domestically, as they currently sit at the foot of the Brazilian top flight with just 10 points from 14 games, and, with their fight for survival briefly on hold, they will be desperate to gain an advantage in the first leg of their round-of-16 tie on Friday.
They welcome an Estudiantes side who cruised through the group stage with relative ease after progressing through qualifying and will look to carry that form over.
The Argentinian side firstly had to take on Audax Italiano and Everton de Vina for a place in the Copa Libertadores, and they advanced with 2-1 and 2-0 aggregate wins respectively.
Los Pincharratas then kicked off their group campaign with a 4-1 thrashing of Velez Sarsfield and a draw with Atletico Nacional, before booking their place in the final 16 with a win over the latter and a pair of victories against Brazilian side Bragantino, keeping three clean sheets in the process.
By the time they were beaten 4-0 by Velez Sarsfield in the final round of fixtures, Ricardo Zielinski's side were already comfortably into the knockout stage, and they will hope to put that defeat behind them after what was an eye-catching run of form on the continent.
Now on the back of consecutive league defeats to Independiente and Newell's Old Boys, Estudiantes will make another trip to Brazil hoping to get the upper hand in their two-legged round-of-16 tie.
Fortaleza Copa Libertadores form:
Fortaleza form (all competitions):
Estudiantes Copa Libertadores form:
Estudiantes form (all competitions):
Team News
Fortaleza's attack should be led by key man Moises, who netted three goals in the group stage including a crucial brace in the win over Colo Colo.
Yago Pikachu is another threat from the right flank, having hit the net 12 times in all competitions so far this season, while contributing two goals and four assists in six Copa Libertadores appearances.
Marcelo Benevenuto is likely to command the back three, with Titi, Tinga and Brayan Ceballos left to fight for the other two spots in Vojvoda's defence.
Estudiantes come into the first leg without full-back Bruno Valdez, who was sent off in their final group game and will serve a suspension as a result.
Veteran forward Mauro Boselli remains a key man in attack, having scored 11 goals in 21 appearances this season, taking his tally to 71 across three different spells for the club.
He could again be joined by Leandro Diaz up front, with the likes of Manuel Castro and Matias Pellegrini battling for starting spots on the wings.
Fortaleza possible starting lineup:
Boeck; Titi, Benevenuto, Tinga; Pikachu, Ronald, Felipe, Capixaba; Lima; Romero, Moises
Estudiantes possible starting lineup:
Andujar; Godoy, Rogel, Noguera, Mas; Rodriguez; Castro, Zuqui, Pellegrini; Diaz, Boselli
We say: Fortaleza 2-1 Estudiantes
While Fortaleza's form on the domestic front has been more than concerning, Vojvoda's men have shown themselves to a different side in South America's premier competition this season, and they will be keen to gain an advantage on home turf.