Diego Simeone's side have overcome Almazan and Arenteiro in this season's competition to advance to this stage, while Real Oviedo have beaten Gimnastica Torrelavega and Granada in the opening two rounds.
Match preview
Real Oviedo last played in La Liga in 2000-01, but they have had a difficult 20 years or so, spending time in the lower leagues in Spain before returning to the Segunda Division in 2015.
The Blues have not progressed past the last-32 stage of the Copa del Rey since 2003, so it would be some story if they were able to navigate their way past Atletico to advance in this season's competition.
Real Oviedo have had to win two matches to advance to this round, recording a 3-2 victory over Gimnastica Torrelavega before beating Granada 1-0 last time out courtesy of a first-half effort from Oier Luengo.
Alvaro Cervera's side have not actually been in action since the 1-0 success over Granada, with their last league game proving to be a 1-0 victory over Sporting Gijon on December 17.
Oviedistas are currently 14th in the Segunda Division table, picking up 27 points from their 21 matches, which has left them six points outside of the relegation zone.
Atletico, meanwhile, will enter this match off the back of a 2-0 win over Elche on December 29, with Joao Felix and Alvaro Morata scoring the goals in the La Liga affair.
The result has left Simeone's side in fourth spot in the table, two points behind third-placed Real Sociedad but only two points ahead of fifth-placed Athletic Bilbao on the same number of matches (15).
Atletico have also played twice in this season's Copa del Rey, recording a 2-0 win over Almazan on November 12 before beating Arenteiro 3-1 on December 22 in the second round.
The Red and Whites were eliminated in the round of 16 last term, and they have only actually won this competition on 10 occasions, with their last success coming back in 2012-13.
The Copa del Rey is likely to represent their best chance of securing silverware this term, though, as they do not have European football in the second half of the campaign, having finished fourth in their Champions League group behind Porto, Club Brugge and Bayer Leverkusen.
Real Oviedo Copa del Rey form:
W
Real Oviedo form (all competitions):
W
W
D
L
W
W
Atletico Madrid Copa del Rey form:
W
W
Atletico Madrid form (all competitions):
D
L
W
W
W
W
Team News
Goalscoring has been a real problem for Real Oviedo this season, with the team only finding the back of the net on 13 occasions in 21 league games, with Borja Baston netting eight of those.
Baston was only a substitute against Granada last time out, but the 30-year-old is likely to be brought into the starting side for this match at the expense of Samuel Obeng.
Head coach Alvaro could otherwise select the same side from the previous round, with Borja Sanchez and Viti Rozada likely to operate in the wide positions for the home team.
Atletico had Mario Hermoso sent off in their 2-0 win over Elche last time out, but the centre-back is available for this match and is expected to be in the starting side.
Simeone will make changes from the side that started in the league, with Sergio Reguilon, Thomas Lemar and Koke likely to come into the XI for this contest.
There should be another start in midfield for Pablo Barrios, though, while Morata is likely to feature in attack, with Felix and Antoine Griezmann potentially dropping to the bench.
Real Oviedo possible starting lineup:
Nadal; Ahijado, Luengo, Calvo, Bretones; Prendes, Suarez; Rozada, Koindredi, Sanchez; Baston
Atletico Madrid possible starting lineup:
Oblak; Gimenez, Savic, Hermoso; Llorente, Koke, Barrios, Koke, Reguilon; Lemar, Morata
We say: Real Oviedo 1-2 Atletico Madrid
Real Oviedo are more than capable of making this an uncomfortable match for Atletico, and we are expecting a close contest on Wednesday. Shocks can happen at this stage of the competition, but Simeone is expected to select a strong side, so Atletico should progress into the last-16 stage of the tournament.