With one side aiming to improve their chances of qualification, and the other apparently bound for Champions League elimination, RB Leipzig will host Aston Villa on Tuesday night.
While luckless Leipzig have lost all five games so far, Villa have accrued 10 points and are still in the mix for a top-eight finish.
Match preview
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After making a scintillating start to their first Champions League campaign - winning three times without conceding a goal - Aston Villa have added only one more point from their last two fixtures in Europe's top club competition.
Amid a dramatic slump in domestic form, the Villans slipped to defeat against Club Brugge in Belgium and then settled for a goalless home draw against injury-depleted Juventus, costing them their top-eight spot in the league phase standings.
Nonetheless, Unai Emery's side have kept four clean sheets from five games so far, and the only time Emiliano Martinez has been beaten was by a Club Brugge penalty in quite bizarre circumstances.
Since being held by Juve last month, the Birmingham club have brought an end to a worrying eight-game winless run across all competitions, recently posting consecutive home triumphs against Brentford and Southampton in the Premier League.
Scorer of Villa's winner against Bayern Munich earlier this season, Jhon Duran netted the only goal in the latter contest, as they scraped past Saints on Saturday, failing to fully capitalise on their dominance but still securing three points.
Often deployed as a 'super-sub', Duran is also his side's top scorer in the Champions League, with two goals, and has attempted more shots (nine) than any of his teammates despite only being on the pitch for 35% of Villa's playing time so far.
Having climbed back into the top half of the Premier League table, Emery's men will now head for Germany knowing that even a draw would surely wrap up a playoff place.
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By contrast, Leipzig are staring an early exit in the face after losing all of their first five fixtures; therefore, only victory will do if they are to have any hope of progressing to the knockout rounds.
Four of those defeats came by a slender one-goal margin against tough opponents - Atletico Madrid, Juventus, Liverpool and Inter Milan - while they were beaten 3-1 by Celtic in Glasgow during a dismal six-game winless streak throughout November.
Ending up empty-handed against Villa would see the Saxony side record their longest losing run in the Champions League - and the longest by any German club since 2003, when Bayer Leverkusen suffered seven defeats on the spin.
Shining brightly despite all those setbacks, star striker Benjamin Sesko has scored three of Leipzig's four goals in the competition this season, and he found the net again at the weekend, as Marco Rose's men beat Holstein Kiel 2-0 in the Bundesliga.
Days after ending their long wait for a win by knocking Eintracht Frankfurt out of the DFB-Pokal, strikes from Sesko and substitute Andre Silva solidified their spot in Germany's top four - Die Roten Bullen sit just three points behind second-placed Frankfurt.
Champions League woes aside, Leipzig have actually lost just three of their last 27 domestic matches while winning 17; however, those defeats have all come during their last five league games, so Rose is still under pressure to disprove his doubters.
Team News
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Missing out on a return to Germany, ex-Leverkusen winger Leon Bailey suffered a hamstring strain during Aston Villa's weekend win over Southampton and now faces a few days on the sidelines.
The visitors otherwise have most of their main men available, as Amadou Onana returned to the squad on Saturday following a foot injury; only Jacob Ramsey (hamstring) joins Bailey in the treatment room at Bodymoor Heath.
Set to start again, England forward Morgan Rogers is one of only five men to reach double figures for completed dribbles (18) and chances created from open play (10) in this season's Champions League, joining an impressive list also featuring Vinicius Junior, Florian Wirtz, Savinho and Johan Bakayoko.
In addition to his European exploits, Jhon Duran has now scored six Premier League goals from outside the box since the start of last season following his latest strike, and the Colombian striker will hope to keep his place ahead of Ollie Watkins.
Meanwhile, Leipzig have a number of absentees, including Castello Lukeba, who serves a one-match suspension and is struggling with a thigh problem in any case.
Influential playmaker Xavi Simons (ankle) is still missing, and Marco Rose must also do without El Chadaille Bitshiabu (muscular), Eljif Elmas (hamstring), Yussuf Poulsen (thigh) and Germany full-back David Raum (ankle).
Up front, Lois Openda has yet to hit the target in Europe this term, after racking up 24 league goals last season, but Rose can also call upon Antonio Nusa - who recorded a hat-trick of assists in last week's cup win - and Benjamin Sesko.
The latter has already scored against Atletico Madrid and Juventus, in addition to three goals and two assists in the Bundesliga, plus five strikes for Slovenia in the UEFA Nations League.
RB Leipzig possible starting lineup:
Gulacsi; Geertruida, Seiwald, Orban, Henrichs; Baumgartner, Haidara, Vermeeren, Nusa; Sesko, Openda
Aston Villa possible starting lineup:
Martinez; Cash, Konsa, Torres, Digne; Kamara, Tielemans; Philogene, Rogers, McGinn; Watkins
We say: RB Leipzig 2-1 Aston Villa
Having pushed some continental heavyweights close without tasting success so far, Leipzig are overdue a first Champions League win of the season.
As Aston Villa's defence is still suspect - and they do not tend to travel well - the talent-packed Bundesliga side should prevail.
For data analysis of the most likely results, scorelines and more for this match please click here.
Jonathan O'Shea
