The back-to-back League Cup winners will be hoping to avoid a huge cup upset to continue their hunt of winning the competition three years on the bounce, whilst Oxford will be hoping to reach the final four for the first time since 1987.
Last time out
The hosts will be hoping for a polar opposite performance to their last outing as they were beaten 1-0 by the struggling Milton Keynes Dons at Stadium MK.
City, however, will be hoping to replicate their most recent performance after they blew away Arsenal at the Emirates Stadium, as a strike from Raheem Sterling and a superb brace from Kevin De Bruyne gave them a comfortable 3-0 win.
Last time they met
The last time these two locked horns came just last year in the same competition as the Premier League Champions avoided an upset to defeat the U's 3-0 at the Kassam.
Goals from Gabriel Jesus, Riyad Mahrez and a first-ever senior goal from Phil Foden gave the Blues the win and put them on their way to win the competition four rounds later.
Despite being just one point off the League One play-off places, Oxford's form has somewhat dipped in recent weeks after the defeat to MK Dons stretched their winless and goalless run to three games, which has included two defeats and a draw.
Pep Guardiola's side head into the game with just one defeat in their last seven in all competitions. However, it still hasn't been the vintage City we have come to know in recent years, with a draw to Newcastle United and defeat to local rivals, Manchester United resulting in them slipping 14 points behind title rivals, Liverpool.
Ones to watch
One man Guardiola may have to be wary of in this one is U's midfielder James Henry. The former Wolves man has scored eight goals and picked up four assists in the league this season, and with City's defence showing some frailties in recent months Henry could be the man to cause the upset.
One man who all City fans will be hoping to see on the team sheet is Phil Foden. The 19-year-old has used his chances in the cup competitions to showcase his undoubted talent, and after positive performances against Dinamo Zagreb and Arsenal in the last week it would be no surprise to see him shining again at the Kassam Stadium.
The main man to watch Henry could potentially miss the Cup clash after he was absent from Saturday's away defeat at Stadium MK. Oxford's injury issues do not stop there as Jamie Hanson, Ben Woodburn, Anthony Forde and Simon Eastwood all remain sidelined for the visit of the Premier League champions.
With a number of injury problems of his own, Guardiola may look to his youth options, with Taylor Harwood-Bellis, Tommy Doyle and Adrian Bernabe all in contention after featuring in the earlier rounds.
Senior players, Sergio Aguero, John Stones, Aymeric Laporte and Leroy Sane have all been ruled out, whilst captain David Silva has also been named a doubt by Guardiola.