Swansea manager Brendan Rodgers is without new signing Leon Britton.
The midfielder, who rejoined the Swans last week, has already featured in the competition this season for Sheffield United and is cup-tied.
Rodgers has hinted he may make changes ahead of the clash with goalkeeper Yves Ma-Kalambay likely to be given a start after only being used in the knock-out games this season.
Striker Stephen Dobbie has had to remain patient in recent weeks but may be given a chance against Orient while new signing Ryan Harley is unavailable after the midfielder returned to Exeter on loan for the rest of the season.
The Swans are hoping to overcome an Orient side buoyant after their victory over Norwich in the last round.
Leyton Orient are sweating on the fitness of skipper Stephen Dawson.
The influential midfielder limped out during the first half of Tuesday night's 2-2 draw against MK Dons with a dead leg.
With Adam Chambers still missing with a hamstring problem, Os boss Russell Slade will be desperate to get Dawson fit in time to travel to south Wales.
Full-back Elliot Omozusi has been sidelined since suffering a hamstring injury in the third-round win at Norwich and remains doubtful, with Andrew Whing likely to deputise again.
Tottenham youngster Tommy Carroll has joined until the end of the season and is eligible along with fellow Spurs loanees Harry Kane and Paul-Jose Mpoku.
Defender Aaron Brown this week joined Stockport on a month's loan.