Meanwhile, their opponents make the trip to the Netherlands looking to end a run of three successive defeats in this competition.
Nevertheless, Erik ten Hag continues to move the club in the right direction, and their 2-2 draw at Atalanta BC on matchday two could prove to be the difference between qualification and demotion to the Europa League.
Ajax let slip a 2-0 advantage in that game, but they remain ahead of the Italian side ahead of an opportunity to record a double over Midtjylland.
Ajax have now gone six matches without defeat in all competitions, their latest victory coming by a 5-0 scoreline at home to Heracles in Sunday's Eredivisie fixture.
Midtjylland have been competitive during their debut appearance in the group stages, proving stubborn opposition for Liverpool before they pushed Ajax ahead of the November international break.
The setback in the reverse fixture was their third successive defeat in all competitions, but Brian Priske's side have responded with the same amount of victories in a row.
While that has been enough to keep the club at the top of the domestic standings, conceding 12 goals from nine matches suggests that they still have improvements to make in defence.
At the other end, forward Sory Kaba has netted in his last two appearances, improving on his previous return of one strike in half-a-dozen outings.
Ajax Champions League form: LDW
Ajax form (all competitions): WDWWWW
FC Midtjylland Champions League form: LLL
FC Midtjylland form (all competitions): LLLWWW
As well as Klaassen, Noussair Mazraoui was also withdrawn with an injury against Heracles at the weekend.
Priske has named the same starting XI for the first three matches in Group D.
Ajax possible starting lineup:
Onana; Klaiber, Schuurs, Martinez, Tagliafico; Labyad, Blind, Gravenberch; Neres, Traore, Tadic
FC Midtjylland possible starting lineup:
Andersen; Andersson, Sviatchenko, Scholz, Paulinho; Onyeka, Cajuste; Dreyer, Sisto, Mabil; Kaba
We say: Ajax 3-1 FC Midtjylland
Facing a four-point deficit, Midtjylland have little choice but to throw caution to the wind on Wednesday evening. However, that will only play into Ajax's favour, and the Dutch giants should have more than enough quality in the final third to record a comfortable win.