While the home side simply have to win and then hope Monagas do not upset Group F leaders Boca Juniors, a draw or even defeat could still see Deportivo make it through to the last 16.
Match preview
After losing to bottom side Monagas earlier this month in Venezuela, Deportivo Pereira still have some work to do in the final fixture of their first group-stage campaign in South America's premier club competition.
Los Matecanas were unable to break down their hosts in Maturin, and a 1-0 defeat gave away the gains made by beating Boca Juniors in late May - as a result, their grip on second place behind the Buenos Aires giants has been loosened.
With seven points from five Group F games so far, Deportivo now lead both unfancied Monagas and Thursday's hosts Colo-Colo by two points in the standings, so a barring an unlikely turn of events at La Bombanera - where the Venezuelans meet Boca - a draw should see them secure their place in the knockout phase draw.
Having been crowned 2022 Finalizacion champions last December, the team from the Andean city of Pereira automatically qualified for this year's Copa Libertadores group stage and have so far made a decent fist of their debut at the elite level.
Now, Alejandro Restrepo's men aim to put aside a mediocre Apertura campaign in Colombia, which ended with a disappointing 12th-place finish, and overcome one of the continent's traditional powers.
Colo-Colo ended a five-year drought to take top spot in Chile last year, thus earning them another crack at winning the Libertadores for a second time - their victory in 1991 still enjoys mythical status in Santiago.
However, the current squad's attempt at traversing Group F has not gone entirely to plan, and coach Gustavo Quinteros saw his side beaten by Boca Juniors for a second time at the start of June, to leave hopes of progress hanging in the balance.
Only if Los Albos now defeat Deportivo Pereira and Boca beat Monagas will they definitely reach the last 16, so the picture is certainly clear before kickoff at Estadio Monumental.
Sitting fifth in the Primera Division following a run of one win from four games, Colo-Colo last featured in the Copa Libertadores knockout rounds back in 2018, when they ultimately reached the quarter-finals.
If they are to repeat that feat this year, the 33-time Chilean champions will need to improve on a meagre goal-haul in the competition so far, having scored only three times in their first five fixtures.
Colo-Colo Copa Libertadores form:
D
W
L
D
L
Colo-Colo form (all competitions):
L
D
W
L
D
L
Deportivo Pereira Copa Libertadores form:
D
L
W
W
L
Team News
Colo-Colo can welcome goalkeeper Fernando de Paul back into their squad for Thursday's game, after he missed the defeat to Boca Juniors due to suspension, having previously been sent off against Monagas.
Brayan Cortes could therefore make way, with De Paul starting behind a three-man back line helmed by Ramiro Gonzalez; at the other end, joint-top scorer Marcos Bolados should start up front.
Carlos Palacios was red-carded earlier in the competition, for a foul on young Boca Juniors defender Valentin Barco, but he could now redeem himself by replacing fellow midfielder Leonardo Gil, who is doubtful due to injury; New Zealand international Marco Rojas is no longer available, having recently left Los Albos.
The visitors, meanwhile, are set to pair Angelo Rodriguez and Arley Rodriguez in attack - the former netted in a 1-1 draw in the reverse fixture against Colo-Colo, while the latter scored Deportivo's winner versus Boca on matchday four.
Since moving to Pereira from Peru's Alianza Lima, Arley has netted five goals in 21 games all told, while veteran defender Carlos Ramirez has matched that tally this term, with one of the 35-year-old's total coming from the penalty spot in last month's win over Group F rivals Monagas.
Colo-Colo possible starting lineup:
De Paul; Gonzalez, Saldivia, D. Gutierrez; B. Gutierrez, Fuentes, Pavez, Bouzat; Palacios; Bolados, Pizarro
Deportivo Pereira possible starting lineup:
Quintana; Quintero, Vasquez, Ramirez; Moreno, Medina, Zuluaga, Fory, Velasquez; Ar. Rodriguez, An. Rodriguez
We say: Colo-Colo 1-1 Deportivo Pereira
As Colo-Colo have not played for three weeks, as their Copa Chile contest against Union La Calera was postponed due to heavy rain, they may fail to find the cohesion required to defeat Copa Libertadores debutants Deportivo Pereira, who could be bound for the last 16.