The Turkish side overcame Randers in the qualifying playoff round to advance to Group E, while Lazio qualified based on their sixth-placed league finish in the Italian top flight last term.
Any hopes of a swift return to the Champions League group stages for Galatasaray were quickly dashed by PSV Eindhoven in the second round of qualifying, with the Dutch outfit easing to a 7-2 aggregate success to force Fatih Terim's side to fight for a Europa League spot.
Galatasaray were handed a scare against St Johnstone but ultimately prevailed to advance to the playoff round, where they marched to a 3-2 aggregate success over Randers - avenging last season's exit to Rangers at that point - as they made the Europa League group stage for only the third time since 2010.
A club of Galatasaray's stature are more used to the bright lights of Tuesdays and Wednesdays in the Champions League, but the 22-time Turkish champions - who prevailed against Arsenal in the 1999-2000 final of Europe's second-string competition - must now battle Lazio, Marseille and Lokomotiv Moscow for a spot in the knockout rounds here.
Terim's side enter their maiden European clash of the season having posted an unbeaten start from their four Super Lig games so far, but they threw away a two-goal lead against Trabzonspor at the weekend, as Emre Kilinc's double was cancelled out by strikes from Andreas Cornelius and Anthony Nwakaeme.
On a brighter note, Galatasaray have struck two goals in each of their four league encounters so far this term, although they have failed to keep a clean sheet in six successive matches at home across all competitions before one of Europe's leading marksmen pays a visit to the Turk Telekom Stadium.
Unable to sustain a Champions League charge during an underwhelming end to the 2020-21 Serie A season, Lazio would not have harboured dreams of another Europa League appearance, but their current coach is no stranger to success in this competition.
After Inter Milan came calling for Simone Inzaghi's signature, 2019 Europa League-winning boss Maurizio Sarri assumed control of the reins at Lazio, but the former Chelsea and Juventus coach's team do not enter this game with the wind in their sails.
Having downed Empoli and Spezia by an aggregate scoreline of 9-2 in the first two gameweeks of the 2021-22 season, Lazio travelled to San Siro to pit their wits against AC Milan but came out on the wrong end of a 2-0 scoreline, with Rafael Leao and Zlatan Ibrahimovic propelling the Rossoneri to victory.
Lazio's run in the 2020-21 Champions League came to an abrupt end when they were dumped out by then-holders Bayern Munich in the last 16, but they have never managed to make it past the quarter-finals of the Europa League in its current format, most recently finishing third in their group with CFR Cluj, Celtic and Rennes in 2019-20.
Galatasaray and Lazio previously locked horns in the last-32 stage of the 2015-16 Europa League, where the Turkish side would stand firm to record a 1-1 draw on home soil before losing 3-1 at the Stadio Olimpico in the second leg.
Reports have claimed that the Brazilian will line up alongside Victor Nelsson - which will see Christian Luyindama drop down to the bench - while Kilinc had to be withdrawn at half time against Trabzonspor and is expected to miss out here due to muscle pain.
The two-goal midfielder joins Sacha Boey, Baris Yilmaz, Sofiane Feghouli, Omar Elabdellaoui and Arda Turan in a well-occupied treatment room, while Brentford loanee Halil Dervisoglu will hope to lead the line.
The visiting coach can afford to go strong ahead of a weekend clash with out-of-form Cagliari, and Lazzari may now be deemed fit enough for a start over Adam Marusic.
Galatasaray possible starting lineup:
Muslera; Yedlin, Nelsson, Marcao, Van Aanholt; Kutlu; Babel, Cicaldau, Morutan, Akturkoglu; Dervisoglu
Lazio possible starting lineup:
Reina; Lazzari, Felipe, Acerbi, Hysaj; Milinkovic-Savic, Basic, Alberto; Pedro, Immobile, Anderson
We say: Galatasaray 0-2 Lazio
Neither Galatasaray nor Lazio got the result they were hoping for in league action at the weekend, and the loss of Kilinc is a bitter blow to the hosts on the attacking front.
While Sarri may ponder some changes in midweek, his visiting side should still have more than enough firepower to get the job done with a clean sheet to boot.
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