Costel Pantilimon could start for the visiting team against a Magpies side hoping to bounce back from a crushing derby defeat at the hands of struggling rival Sunderland.
Alan Pardew's side slumped to a 2-1 defeat in the Tyne-Wear derby against Sunderland at the Stadium of Light on Sunday, a result which gave the club's biggest rival its first league win of the season.
Mathieu Debuchy thought he had rescued a point for the Magpies when he canceled out Steven Fletcher's early opener, but a superb late strike from Fabio Borini handed Sunderland all three points in Gus Poyet's first home game in charge.
The defeat is typical of Newcastle's inconsistent start to the campaign, which has seen the club win five and lose four of its 11 fixtures in all competitions.
One of those reverses came at City on the opening weekend of the Premier League season, when Manuel Pellegrini's men ran riot in a 4-0 victory.
Pardew has no fresh injury worries ahead of Wednesday's clash at St James' Park. Ryan Taylor [knee] remains a long term absentee, while Fabricio Coloccini is unlikely to be risked as he continues his recovery from a groin injury.
Pellegrini, meanwhile, will also look to get his charges back on track after they fell to their third Premier League defeat of the season in a 2-1 defeat to fellow title hopefuls Chelsea on Sunday.
Sergio Aguero looked to have earned City a draw when he equalized Andre Schurrle's first half opener, but a mix-up between Joe Hart and Matija Nastasic allowed Fernando Torres to tap home a late winner.
Hart is likely to be rested in the cup clash at St James' Park, with Costel Pantilimon expected to step in for the visiting side.
Captain Vincent Kompany will be unavailable for the fixture, meanwhile, as he continues his comeback from a thigh injury.
City hammered Wigan Athletic 5-0 in the round three of the Capital One Cup, while Newcastle has defeated Morecambe and Leeds United to make it to this stage.