The two teams, who are joined in Group F with Club Nacional and Argentinos Juniors, will be looking to open their accounts with three points at the Estadio Atanasio Girardot.
Atletico Nacional qualified for the group stages of the Copa Libertadores for the first time in four years courtesy of beating Paraguayan side Club Libertad over two legs.
Despite losing the first leg 1-0 and also conceding an early goal in the second leg, El Verde fought back and secured a comfortable 4-1 victory last Thursday, winning 4-2 on aggregate, thanks to goals from Jarlan Barrera, Baldomero Perlaza, Jonathan Alvez and Jefferson Duque.
Nacional, the most successful club in Colombia with 16 top-flight titles, have enjoyed a successful domestic campaign so far this season, finishing top of the Categoria Premiera A and progressing into the quarter-finals.
Last weekend saw El Verde blitz past Patriotas Boyaca, with four goals from Duque helping Alexandre Guimaraes's side win 7-1 on home soil.
Nacional now turn their attention back to the Copa Libertadores, a competition they have won twice before in 1989 and more recently in 2016, beating Ecuadorian side Independiente de Valle 2-1 in the final.
Guimaraes is hoping he can guide El Verde to another final and a victory on Thursday would be the perfect way to begin their 2021 campaign.
After winning their third successive top-flight title last season, Universidad Catolica automatically qualified for the group stages of this year's Copa Libertadores.
The 15-time Chilean Primera Division champions sit top of the table once again this campaign after winning three of their opening four matches, including a 2-1 victory over Curico Unido last weekend.
In the last two seasons, Catolica were in the group stages of the Copa Libertadores but finished third on both occasions, narrowly missing out on a place in the round of 16.
The Santiago-based outfit have only ever reached the final once before back in 1993, but former Chelsea and Tottenham Hotspur midfielder Gus Poyet, who took charge of the club in February, is hoping that his new side can improve on performances in recent years and become a force to be reckoned with in South America.
Brayan Cordoba and Geisson Perea could keep their partnership at centre-back ahead of Yerson Mosquera and Emanuel Olivera, while Danovis Banguero is expected to return at left-back at the expense of Nicolas Hernandez.
Duque, who has scored 12 goals in 20 appearances so far this season, is likely to start as the lone striker ahead of Alvez.
For Universidad Catalica, former Real Betis and Sporting Kansas City midfielder Felipe Gutierrez, who has yet to play for the club since joining earlier this year, is ruled out for around three months with a serious knee injury.
Atletico Nacional possible starting lineup:
Mier; Marulanda, Cordoba, Perea, Banguero; Rovira, Londono; Perlaza, Barrera, Andrade; Duque
Universidad Catolica possible starting lineup:
Dituro; Fuenzalida, Astaburuaga, Huerta, Parot; Buonanotte, Saavedra, Aued; Valencia, Zampedri, Lezcano
We say: Atletico Nacional 2-0 Universidad Catolica
Both Atletico Nacional and Universidad Catalica head into Thursday's clash in good form, with the Colombian side having scored 11 goals in their last two matches and the visitors winning four of their last five games.
The hosts will be slight favourites for this encounter, and we feel that they have enough quality to secure all three points in Medellin.