The American was confirmed to be out for at least eight weeks as he recovers from a hamstring injury sustained against Peterborough United.
The game will also be a step too soon for defender Dara O'Shea who played 45 minutes in the PL2 loss to Birmingham City under 23's on Monday afternoon.
The Super Eagles were knocked out of the competition at the last-16 stage after defeat to Tunisia, meaning Ajayi is free to continue his Albion duties.
Preston are missing Josh Murphy whose return should be imminent following an ankle injury back in October. Midfielder Daniel Johnson will be unavailable after being called up to the Jamaica squad this week.
However, the Lilywhites will be boosted by the signing of Aston Villa loanee Cameron Archer who joined earlier this week.
(3-4-3) Johnstone, Clarke, Bartley, Kipre, Townsend, Livermore, Mowatt, Furlong, Grant, Robinson, Diangana
(3-4-1-2) Iversen, Bauer, Van De Berg, Cunningham, Rafferty, Whiteman, Ledson, Barkhuizen, Browne, Evans, Jakobsen.
Preston are without a win in three EFL Championship games and currently sit 15th in the league.
Their away form provides pretty awful viewing for North End fans as they boast the fifth-worst away record in the league.
In their last game, Lowe's outfit were edged out by Swansea City and they'll be looking to right the wrongs of that defeat this Wednesday.
Meanwhile, the Baggies will be hoping to build on an impressive victory over Peterborough United after scoring three times in 12 minutes to win the game.
Still unbeaten at home too, Ismael's side will aim to continue their resilient defensive record at The Hawthorns - only conceding six so far.
And whilst they're still seven points away from Blackburn Rovers in the automatic promotion spots, Wednesday provides a glistening opportunity for them to gain more ground on the top two.
Ones to watch
The winger produced a stellar substitute appearance off the bench in Albion's last match.
The former West Ham United man came on for the injured Dike after 53 minutes and changed the game for Ismael's side.
Grabbing a goal late on, the 23-year-old gave the supporters a glimpse of the player that propelled them towards Premier League promotion back in 2020.
The youngster has signed for the Lilywhites on a loan deal until the end of the season and will look to provide a goalscoring touch alongside Emil Riis Jakobsen.
Only 20 years old, he'll be looking for goals to impress first-team boss Steven Gerrard.
How to watch
Audio coverage will be available for those in the UK and Ireland via WBATV and iFollow. There'll also be a stream available for paying Sky Sports customers on the red button. Kick-off on Wednesday is set for 20:00 GMT.