Xeka and Benjamin Andre are both suspended for the first leg after reaching the limit for bookings in Lille's final Europa League group game.
Sven Botman didn't play against Brest at the weekend but will surely return to the starting XI here.
Renato Sanches has only started one game in 2021 due to injury sustained late last year but may be required here with both Andre and Xeka banned. Boubakary Soumare will take one spot in central midfield.
Yusuf Yazici isn't a regular starter in the league but scored two hat-tricks in the Europa League group stage and should lead the line here with Jonathan David.
Mehmet Zeki Çelik or Jeremy Pied will start at right-back for the hosts.
Ajax remarkably forgot to include club record signing Sebastien Haller in their Europa League squad for the knockout stage. Andre Onana is suspended for breaching anti-doping regulations.
With Haller unavailable, it wouldn't be a surprise to see Dusan Tadic deployed centrally rather than Lassina Traore so both David Neres and Antony can play out wide.
Left-back Nicolas Tagliafico was fit enough to start Ajax's win away to Heracles at the weekend in a boost for the Dutch side, but right-back Noussair Mazraoui was forced off injured having gone into the match as a doubt.
18-year-old Devyne Rensch is on standby to make his European debut from the off should Mazraoui not recover in time.
Lille are surprise leaders in France, one point clear of Paris Saint-Germain despite dropping points at the weekend. The Ligue 1 side had won seven in a row prior to a goalless draw on Sunday. They've only lost once at home in all competitions this season.
Ajax haven't lost in any competition since before Christmas. The Dutch giants are unbeaten in their last 13 and have won eight in a row. They are, however, weakened by the absence of No.1 goalkeeper Andre Onana and club-record signing Sebastien Haller.
LIVE STREAM - CLICK HERE