A last-gasp own goal saw the Brazilian outfit escape from the home leg with an advantage, but that will be put to the test when they go on their travels to finish the job.
Match preview
Club Libertad qualified through a tough Copa Sudamericana group, finishing with an impressive tally of 13 points from six games with Atletico Goianiense, Newell's Old Boys and Palestino.
They met Colombian outfit Junior in the round of 16, and came out of a dramatic away leg with a 4-3 win, as Hector Villalba hit an early brace before Julio Enciso and Hugo Martinez found the net to put them back ahead and carry an advantage into the second leg.
Daniel Garnero's side stood strong to defend their lead, and while Junior found the net late in the second game, a 1-0 win was not enough as Libertad progressed on away goals, booking their quarter-final tie with Santos.
They made the trip to Brazil for the first leg, and while the hosts took the lead through Carlos Sanchez, a two-minute spell seeing Santos reduced to 10 men and Libertad draw level through Daniel Bocanegra provided huge optimism for the final 30 minutes, only for the Brazilian giants to go back ahead in the dying minutes through an Alexander Barboza own goal and bring a one-goal lead into Friday's game.
Following the disappointment of that first leg and a recent league draw, with 12 de Octubre holding Garnero's men to a point with an injury-time equaliser to see the game finish 3-3, Libertad will be desperate to overturn the deficit and continue their Copa Sudamericana journey by progressing through to the final four.
Meanwhile, Santos will arrive in Paraguay with the aim of defending the lead that they managed to snatch in the dying minutes of their home leg, having battled through the majority of the second half with 10 men.
Unlike their opponents, Santos did not qualify through the group stage, instead dropping into the round of 16 after finishing third in their Copa Libertadores group stage.
Despite picking up a dominant 5-0 win over The Strongest and a 1-0 victory over Argentinian giants Boca Juniors, the Alvinegro would lose their other four games, meaning they could not break into the top two and the Copa Libertadores group stage, although they did pip The Strongest to third spot allowing qualification for the Copa Sudamericana round of 16.
They faced a tough test in the opening knockout game, taking on Argentinian side Independiente in the round of 16, and a narrow 1-0 home win fired them to a 2-1 aggregate victory, with Kaio Jorge hitting a goal in each match.
That saw them progress to this stage, and Fernando Diniz will gear his side up to keep hold of their lead in order to book their place in the semi-finals and take a huge step closer to the title.
Club Libertad Copa Sudamericana form:
Club Libertad form (all competitions):
Santos Copa Sudamericana form:
Santos form (all competitions):
Team News
Given their need for goals, Club Libertad may call upon experienced forward Oscar Cardozo, who has 54 Paraguay caps and 12 international goals to his name, while also having hit 58 goals in 136 appearances for the club after previously netting 112 goals in a successful spell at Benfica.
Daniel Bocanegra also brings experience in the middle, while Ramon Martinez could be the midfielder sacrificed to allow for another attacking spot.
Santos come into the game without centre-back Kaiky Fernandes, who will serve a suspension after he was shown a red card in the first leg.
In his absence, Wagner Leonardo should come in to partner Luiz Felipe at the heart of the back four.
The threatening trio of Carlos Sanchez, Gabriel Pirani and Lucas Braga should again feature, likely supporting Marcos Guilherme as a lone striker.
Club Libertad possible starting lineup:
Silva; Mayada, Viera, Barboza, Vangioni; Villalba, Bocanegra, Martinez, Melgarejo; Cardozo, Ferreira
Santos possible starting lineup:
Paulo; Madson, Filipe, Leonardo, Jonatan; Camacho, Mota; Sanchez, Pirani, Braga; Guilherme
We say: Club Libertad 1-1 Santos (Santos win 3-2 on aggregate)
Santos certainly face a tough test as they arrive in Paraguay with a slender lead to defend, but we see them narrowly escaping with an aggregate win.
Libertad will put the Brazilian outfit on the back foot, and will have their chances to win the game, but we would not look past Santos getting a goal of their own to stay in front.