A 3-0 win in the first leg in Ecuador last week makes Quito the heavy favourites to face either Corinthians or Fortaleza in the final.
Match preview
Defensa struggled massively in the Ecuadorian capital a week ago, and may have given themselves too much of a mountain to climb.
Hitting a rocky run form at exactly the worst time means the 2020 Sudamericana champions may miss out on the chance to compete in another final.
Before last week, Julio Vaccari's men had gone on a 10-game unbeaten streak, but prepared for the first leg of this tie with a defeat at Central Cordoba.
Defensa were then hapless in Quito, going down 3-0, before losing again at the weekend against an Arsenal Sarandi side which finished bottom of the Primera Division.
A sixth-placed finish means Defensa will play Sudamericana football again next season, but the chances of them upgrading to the Copa Libertadores with silverware in this competition now appears slim.
Quito will gladly seek a repeat of last year's result here, when the Ecuadorian side won 2-1 in Buenos Aires in the group stage.
There is much more on the line this time around, but Quito would not even need heroics like that thanks to the work they got done at home.
After edging through the two previous rounds on penalties over Sao Paulo and Nublense, Luis Zubeldia's side are in complete command here.
Quito have lost both of their second leg encounters this season, but even another one-goal defeat would be more than enough here.
This would be their first final since 2011, a season which saw them finally lose their grip on South American continental football.
Quito won the Sudamericana in 2009, a year after winning the Libertadores against all odds, and then reaching the Club World Cup final.
In a domestic league where Quito have lost just one of their last 15 games, they were given the weekend off to focus solely on getting the job here.
That means their game with Universidad Catolica will now be moved, and that could have provided them with a strong test and a major distraction, considering they are 14 games unbeaten themselves.
Defensa y Justicia Copa Sudamericana form:
W
W
W
D
W
L
Defensa y Justicia form (all competitions):
D
W
W
L
L
L
LDU Quito Copa Sudamericana form:
W
W
W
W
W
W
LDU Quito form (all competitions):
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Team News
Top scorer Nicolas Fernandez was a huge miss in the first leg, and will be so again here as Defensa look to overturn a huge margin.
Eight goals in this competition has Fernandez second in the scoring charts, but he has now missed the last three games and Defensa lost all three of those.
Along with Fernandez, Kevin Gutierrez will also miss out for the hosts as he recovers from a knee injury.
Gaston Togni should come back into the starting XI, after not featuring at all before the first leg and playing just 36 minutes at the weekend.
No player in the Sudamericana has contributed to more goals than Togni's 11 - five goals, six assists.
Paolo Guerrero only joined Quito in August, but the Peruvian has also scored two of the most important goals this club has seen in over a decade - netting a brace in the first leg.
The 39-year-old's only other goal prior to last week also came in this competition, but his game time had been managed in preparation for this tie.
Alexander Alvarado will be available after sitting out the first leg because of his sending off at Sao Paulo in the quarter-final.
Defensa y Justicia possible starting lineup:
Bologna; Tripichio, Malatini, Ramos, Caceres; Lopez, Soto, Barbona; Solari, Pratto, Togni
LDU Quito possible starting lineup:
Dominguez; Quinteros, Ade, Rodriguez, Quinonez; Martinez, Piovi, Gonzalez; Ibarra, Guerrero, Julio
We say: Defensa y Justicia 2-1 LDU Quito
With all the pressure heaped onto the visitors who will try to hold onto a three-goal lead, Defensa should be free to go all out for the win.