With the Primera Iberdrola curtailed and Barcelona awarded the title, the UEFA Women's Champions League will be the first professional match for both sides since March.
Barcelona reached the final of the competition last year only to be defeated 4-1 by Olympique Lyon in Budapest. The winner of Friday's game will face either Glasgow City or VfL Wolfsburg in the semi-finals.
Speaking to VAVEL UK ahead of the game, Barcelona striker Asisat Oshoala said that her side will not take this game lightly, despite their good record against Atleti:
"Atletico Madrid are a very good team and a top side as well. The fact that we beat them doesn't mean that it's going to happen again. They're a very good side.
"We just have to keep working on ourselves to get better than before, to make sure we try to get something out of the game, so it's going to be a tough one. I think we're just going to give our best.
"I'm not going to say anything more because you have to learn to respect the opponent you know and if not, it's going to cost you the game."
Atletico Madrid have named Hedvig Lindahl, Alia Guagni, Merel van Dongen, Jade Moore, Turid Knaak and Evelyn Laurent to their squad as their six new transfers.
'Atleti' have been hit with a list of players who have tested positive for COVID-19 and will thus not be able to travel to Bilbao, with Deyna Castellanos, Leicy Santos, Laia Aleixandri, Charlyn Corral and Silvia Meseguer all unavailable.
The only notable addition to FCB's side is Ana-Maria Crnogorcevic, while the Catalonians have also included several youngsters in their team to make up for recent departures.
Ones to watch
Atletico Madrid - Ángela Sosa
Having scored 27 goals in the last three seasons and being named as the league's MVP in the 2018/19 season, Sosa may be one to keep your eye on in Friday's game.
She scored what would prove to be the decisive goal in the previous leg against Manchester City where Atleti were 3-2 victors on aggregate.
Although she did not receive a callup to the Women's World Cup last year, her performances earned her a place in Spain's SheBelieves Cup squad this season.
FC Barcelona - Jennifer Hermoso
The Primera Iberdrola's top scorer across the 2019/20 campaign with a total of 23 goals, Hermoso will be one of the main goalscoring threats for Barca.
Usually playing in a false nine or an attacking midfielder, Hermoso's main threat comes when playing in between the opposition lines.
Hermoso is in her second spell at Barcelona, having played for four years between 2013 and 2017 and rejoining the club in last summer's transfer window.
As well as Hermoso, Nigerian Asisat Oshoala could be one to watch for Barcelona and was second-top scorer this season.
The two last faced in the semi-finals of the Spanish SuperCup, where Barca were 3-2 victors.
Barca won the first game between the two in the Primera Iberdrola 6-1, while the other was a scoreless draw.
Where to watch on TV and Stream
Atletico Madrid vs FC Barcelona will kick off at 17:00 BST on Friday.
For those in the UK and Ireland, the game is available to be watched on BT Sport 3 or via the BT Sport App
Viaplay will be showing the match in Nordic nations, while Eleven Sports have the rights to show it in Portugal. Gol will be showing it in Spain and ESPN are the broadcaster for Brazil.
CBS All Access have purchased the rights and will be showing all UWCL matches in the United States
For all other international viewers, the game will be available on BarcaTV+ and UEFA TV.