The Paraguayan club seek an outcome that puts them in good stead for the reverse fixture in Brazil next week.
Match preview
Libertad hope to outdo Fortaleza to make it to the competition's quarter-finals, having dispatched Tigre in the knockout round playoffs.
A 2-1 victory at the Estadio Tigo La Huerta was followed by a 1-0 triumph away from home to secure a 3-1 aggregate success over the Argentine Primera Division side.
A similar outcome in the round of 16 will be welcome, although Daniel Garnero would hope to avoid the repeat of the slow start seen in the first leg against Tigre — the Cabbage Growers came from behind to secure a 2-1 victory.
Libertad struggled for home results in the Copa Libertadores, losing twice and playing out a draw, but could gain confidence from that triumph over their playoff opponents.
Garnero's team head into Tuesday's game on the back of a 2-0 league triumph over Sportivo Ameliano on Sunday, extending a winning run in all competitions to six.
The away side are Fortaleza, whose run to this stage in this season's Sudamericana has been commendable.
Juan Pablo Vojvoda's team have won five of six games (one defeat) en route to this stage, with the club's only loss coming in their penultimate group game against Estudiantes de Merida.
Be that as it may, Fortaleza's recent form is concerning due to three defeats on the trot and four losses in their last five games.
The only win for Tricolor in that period was a 1-0 triumph over Athletico Paranaense in early July, a game decided by an 84th-minute winning goal from Yago Pikachu.
Indeed, Vojvoda's team are underdogs in their last 16 tie against Libertad, but it will be interesting to see if the Brazilian side show something different on Tuesday.
Club Libertad Copa Sudamericana form:
W
W
Club Libertad form (all competitions):
L
W
L
D
W
W
Fortaleza Copa Sudamericana form:
W
W
W
W
L
W
Fortaleza form (all competitions):
W
L
W
L
L
L
Team News
Antonio Bareiro's recovery from a cruciate ligament rupture continued over the weekend, with a goal against Sportivo Ameliano, and the wide forward could start on Tuesday.
Like Bareiro, Bautista Merlini returned from a ruptured ligament injury, although the former's first outing since last year came on in the win over Clasura opponents; a place on the bench is likely in the Sudamericana game.
Hugo Martinez is not expected to feature, with a muscle injury ruling out the central midfielder from the round of 16 fixture this week.
A ruptured knee ligament means Pedro Rocha will not play again this season; likewise, Hercules, whose cruciate ligament rupture could rule him out until 2024.
Tomas Pochettino (four) and Pikachu (five) have contributed to more goals than any player at Fortaleza in this year's tournament, and the pair should play a significant part in Tuesday's outcome.
Vojvoda is expected to utilise a back four, even if he could opt for a 4-3-3 or 4-2-3-1, as seen recently in the Brasileiro.
Club Libertad possible starting lineup:
Silva; Piris, Viera, Barboza, Espinoza; Bareiro, Sanabria, Campuzano, Villalba; Cardozo, Melgarejo
Fortaleza possible starting lineup:
Ricardo; Dudu, Benevenuto, Titi, Pacheco; Weilson, Sasha, Pochettino; Pikachu, Lucero, Marinho