The Chilean side will be hoping to lift the trophy for the first time in their history, in what will be their seventh appearance in the competition.
Match preview
Currently sixth in the Chilean Primera Division after 19 matches, the Baisanos return to Copa Sudamericana action following a 3-2 aggregate victory over Cuiaba in the previous round.
Lucas Bovaglio's side reached this second-tier competition after finishing third in Copa Libertadores group E and will now aim to go all the way.
This will be the first-ever meeting between Palestino and Independiente Medellin in this competition, having previously faced each other in the knockout stages of the Copa Libertadores, where the Arabes emerged victorious on penalties after a 2-2 draw over two legs.
Palestino enter this encounter buoyed by a resounding 4-1 league win over O'Higgins FC and will look to make it back-to-back victories - however, the Chilean side have been inconsistent at home, winning three, losing two, and drawing one of their last six matches.
Independiente Medellin, on the other hand, will be seeking to continue their impressive Copa Sudamericana form which saw them top group A with four wins, one draw, and one defeat.
The visitors parted ways with former manager Alfredo Arias earlier this month, appointing Alejandro Restrepo in his place, and Restrepo will aim to lead the team to their first-ever Copa Sudamericana title, with their best previous finish being the quarter-finals in 2016.
The Colombian side have endured a difficult start to the second half of their domestic campaign, currently 11th in the table with just one win from five matches, alongside three draws and one defeat.
While Independiente were perfect at home during the group stages of this competition, they were less impressive on the road, losing one and drawing one of their three away matches.
El Decano have also struggled on their travels heading into this match, failing to win any of their last three, drawing two and losing the most recent.
Palestino Copa Sudamericana form:
D
W
Palestino form (all competitions):
W
W
D
L
D
W
Independiente Medellin Copa Sudamericana form:
L
W
W
W
D
W
Team News
Palestino will be without 22-year-old midfielder Nicolas Meza for this match, as he recovers from a cruciate ligament tear.
Bryan Carrasco is Palestino's top scorer in the league with seven goals, making him a key player to watch.
Independiente Medellin have a full squad available for selection, giving manager Restrepo plenty of options.
Brayan Muniz, who scored six goals in the group stage, will be aiming to increase his tally for Independiente Medellin.
Palestino possible starting lineup:
Rigamonti; Rojas, Vejar, Suarez, Zuniga; Linares; Carrasco, Palacio, Davila, Benitez; Marabel
Independiente Medellin possible starting lineup:
Mosquera; Marulanda, Palacios, Moreno, Londono; Torres, Loaiza, Quinones; Monsalve, Cuesta, Muniz