On Sunday, Villa produced one of their standout performances of the season to secure a 2-1 victory against Arsenal in the Premier League.
However, that has not stopped the Spaniard from tinkering with his side, bringing Matty Cash and Douglas Luiz back into his starting lineup.
While Luiz was suspended for the fixture at the Emirates Stadium, Cash is making his first appearance since March 17 due to injury.
Diego Carlos and Morgan Rogers are the players to drop out of the team, Ezri Konsa moving in-field to partner Pau Torres in central defence.
Lille make just one change from first leg
Meanwhile, Paulo Fonseca has made the decision to make just the one change to his Lille starting lineup for the game in France.
Lille are well rested having had a weekend off from Ligue 1 action, but Edon Zhegrova is absent from the team due to injury.
Yusuf Yazici has been recalled to the team in his place, the Turkish player taking his spot on the right flank.
In-demand Leny Yoro, as expected, is selected in defence, while Jonathan David leads the line.
Lille: Chevalier; Santos, Diakite, Yoro, Ismaily; Andre, Bentaleb; Yazici, Haraldsson, Gudmundsson; David
Subs: Alexsandro, Bouaddi, Cabella, Cavaleiro, Ferrah, Gomes, Mannone, Morais, Negrel, Ounas, Toure
Aston Villa: Martinez; Cash, Konsa, Torres, Digne; Zaniolo, McGinn, Luiz, Tielemans, Diaby; Watkins
Subs: Olsen, Gauci, Carlos, Lenglet, Duran, Rogers, Kesler-Hayden, Bailey, Iroegbunam, Munroe, Kellyman