Les Dogues booked their place in the group stage after marching to the top-flight title last term, while their visitors took fourth spot in the Bundesliga.
Match preview
Attempting to emulate Christophe Galtier - who is now working his magic at Nice - was going to be a tough act to follow for Jocelyn Gourvennec at Lille, but the reigning French champions are simply a shadow of their former selves.
After getting off the mark in Ligue 1 at the fourth attempt against Montpellier HSC before the international break, Les Dogues travelled to Lorient on Friday night aiming to extend their unbeaten away run in the league to 17 matches, while their hosts sought to win their sixth home game in a row.
In the end, Lille's resistance on the road was broken, as Armand Lauriente and Terem Moffi netted either side of Burak Yilmaz's penalty to condemn Les Dogues to a first league defeat away from home since November 2020, which only serves to increase the pessimism in the champions' ranks.
Gourvennec may have kicked off his competitive reign with victory over Paris Saint-Germain in the Trophee des Champions, but his side have only won two of their six competitive fixtures ahead of their first Champions League game since December 2019.
Five of Lille's six appearances in the Champions League proper have ended in the group stage, and Les Dogues enter Tuesday's game having failed to win any of their last nine in the competition since a 2-0 win over Grasshopper in the 2014-15 qualifiers, while their last group-stage win came all the way back against BATE Borisov in 2012.
After enjoying their best Bundesliga season since their second-placed ranking in the 2014-15 campaign, Wolfsburg continue to thrive under new coach Mark van Bommel, who has overseen a near faultless start to his side's 2021-22 campaign.
Achieving automatic qualification for the Champions League group stage via a fourth-placed finish last term, the German giants secured their fourth win from as many matches in the league on September 11, as Lukas Nmecha and Wout Weghorst increased their tallies for the season during a 2-0 win over Greuther Furth.
Victories over RB Leipzig, Hertha Berlin and Bochum - with a total of six goals scored and only one conceded - have also helped to propel Van Bommel's side to the top of the Bundesliga rankings as the only side to have maintained their 100% record so far.
However, the challenge of juggling Bundesliga and Champions League commitments starts now for Wolfsburg, who most recently suffered defeat to Real Madrid in the quarter-finals of the 2015-16 tournament, although they did beat Los Blancos 2-0 at home that year before a 3-0 defeat at the Bernabeu.
Lille and Wolfsburg previously locked horns in the group stage of the 2014-15 Europa League, during which the German giants were held to a 1-1 draw at home before cruising to a 3-0 success on the road, where now-Torino left-back Ricardo Rodriguez bagged a brace.
Lille form (all competitions):
Wolfsburg form (all competitions):
Team News
Lille lost Domagoj Bradaric, Timothy Weah and Jonathan Bamba to injury before the defeat to Lorient, although the latter two are closer to returns, while Renato Sanches is expected to miss another two weeks at least.
Right-back Zeki Celik also did not take part against Lorient due to calf pain but is not thought to be nursing anything serious, and the Turkey international should displace Tiago Djalo if he is passed fit.
Jonathan David rejoined the group for Friday's defeat despite only arriving back on the morning of the game, and the Canada international is in line to return to the first XI after a 15-minute cameo at the Stade du Moustoir.
As for Wolfsburg, full-backs Kevin Mbabu and Jerome Roussillon both made the bench against Greuther Furth, but Xaver Schlager, Bartosz Bialek and William are all long-term absentees with knee problems.
Paulo Otavio's ankle problem will also render him unavailable for this game, while John Brooks was fit enough for a substitute outing at the weekend and could push Sebastiaan Bornauw for a place alongside the highly-rated Maxence Lacroix.
Renato Steffen and Dodi Lukebakio are both options for change in the wide areas for the visitors, who should keep Maximilian Arnold and Josuha Guilavogui as an effective midfield pairing.
Lille possible starting lineup:
Grbic; Celik, Fonte, Botman, Reinildo; Ikone, Andre, Xeka, Yazici; David, Yilmaz
Wolfsburg possible starting lineup:
Casteels; Baku, Lacroix, Brooks, Roussillon; Arnold, Guilavogui; Nmecha, Philipp, Steffen; Weghorst
We say: Lille 1-2 Wolfsburg
Wolfsburg are clearly the ones with the wind in their sails heading into this opening clash, with Van Bommel's side producing defensive masterclasses week in week out and boasting quite the plethora of attacking talent.
Lille will be determined to put their Ligue 1 troubles behind them for a few days at least, but we can envisage Gourvennec's struggles continuing with a narrow defeat in front of the home crowd.