Both Manchester United and Juventus will be looking to get some succour from Europe after disappointing results in their domestic leagues at the weekend while Welsh star Gareth Bale could make only his second start of the season for Real Madrid after a succession of niggling injuries:
Bayer Leverkusen (GER) v Shakhtar Donetsk (UKR)
Leverkusen limbered up for this match in controversial fashion, beating Hoffenheim 2-1 courtesy of a 'phantom' goal - Stefan Kiessling heading the winner via a hole in the side netting.
While the Bundesliga powers that be mull over what to do about the result Leverkusen are lying third, one point behind Bayern Munich, their best ever domestic start.
Rolled over by Manchester United in their Group A opener the Germans got their European bid up and running at the second attempt, against Real Sociedad.
Shakhtar, second only on goal difference to United, will be keen to dispel memories of last season's trip to Germany when the wheels came off their campaign with a 3-0 last 16 loss at Borussia Dortmund.
The Ukrainian champions, appearing at the group stage for the fourth successive season, have begun brightly with a win over Real Sociedad and a draw against United.
Manchester United (ENG) v Real Sociedad (ESP)
United may be enduring a torrid start to the Premier League, the weekend draw with Southampton leaving the titleholders in unusual territory - eighth place and their worst start in 24 years. Europe has proved more forgiving, with David Moyes' side topping Group A on goal difference after the Leverkusen win and Shakhtar stalemate.
Pointless Real need to leave Old Trafford with something if they are to inject some life into their first CL campaign in a decade. Whatever happens the outcome is unlikely to be as harsh as their only previous visit to England, when they crashed 6-0 at Liverpool in the 1975/76 UEFA Cup.
They received a welcome boost for this first ever meeting between the two teams with a 2-1 win over Valencia in La Liga at the weekend.
Real Madrid (ESP) v Juventus (ITA)
Real Madrid are sailing regally to the knockout stages, the Spaniards' topping Group B after crushing defeats of FC Copenhagen and Galatasaray. Real could field Gareth Bale, who returned to action after minor injuries as a late substitute in Saturday's 2-0 win over Malaga which left Carlo Ancelotti's men in third. Juve's visit precedes the first 'el clasico' of the season with a trip to Barcelona looming at the weekend. Xabi Alonso, sidelined since fracturing a foot in August, is full recovered but unlikely to be thrust straight back into the fray.
With two draws Juve are waiting for their first win, and hardly had the best preparations for the trip to the Bernabeu a 4-2 loss, their first of the season, to Fiorentina. Coach Antonio Conte spoke about "a massive test', adding: "Madrid are arguably one of the most ambitious teams. We're facing a club that really want this title, because of their history and their hunt for a tenth European Cup."
Galatasaray (TUR) FC Copenhagen (DEN)
Both teams, with one point apiece, are out to bag their first wins in Istanbul. Galatasaray picked themselves up from an opening drubbing by Real to share the spoils with Juventus. Having made it into the knockout stages last season they need to get moving if they are to have any hope of repeating that feat this time against Danish champions Copenhagen.
Anderlecht (BEL) v Paris Saint Germain (FRA)
Paris Saint Germain should be anticipating a third successive win in three Champions League games as they face an Anderlecht side devoid of confidence and pointless. Ligue 1 leaders after trouncing Bastia at the weekend PSG will be without defender Christophe Jallet, Javier Pastore and Thiago Silva, all injured but such are the riches at coach Laurent Blanc's disposal that their absences shouldn't matter. Anderlecht coach John van den Brom sent out the youngest team in the club's history for the 2-0 league win over Mons last Friday and could well do the same on Wednesday where out of form skipper Guillaume Gillet is likely to start on the bench.
Benfica (POR) v Olympiakos (GRE)
Both these sides will see the outcome of their two matches as pivotal as to who finishes second and a place in the knockout phase. Both have one win to their credit in the opening two games, over hapless Anderlecht. Benfica will fancy their chances for this game as they have won their last seven European home matches while Olympiakos have yet to beat Portuguese opposition away and have not managed a goal in five trips to Portugal. Olympiakos have been in imperious form in their own league, winning seven and drawing one of the matches, the latest a 4-1 away win against Platanias on Saturday.
CSKA Moscow (RUS) v Manchester City (ENG)
Both will fancy their chances of taking the runners up spot with Pilsen pretty much out of the running and while City have a woeful away record losing five of their six Champions League away games in the past two campaigns they have a chance of recording their second successive away win this season as CSKA have a poor home record, taking just three points from a possible nine in their last appearance in the CL in 2011/12. City warmed up with a psychological boosting first away win in the Premier League on Saturday, 3-1 at West Ham with Sergio Aguero key to the victory. City manager Manuel Pellegrini believes he now has the squad strength to make an impact both domestically and on the continent. CSKA by contrast are now winless and goalless in their last five domestic matches and without playmaker Alan Dzagoev, who is injured.
Bayern Munich (GER) v Viktoria Pilsen (CZE)
Holders Bayern should have little trouble in making it nine points from three games against pointless Pilsen although coach Pep Guardiola wants to see a marked improvement in their first-half displays which have been generally lethargic all season. The hosts, though, will be missing Swiss midfielder Xherdan Shaqiri and Brazilian defender Dante, who are both injured, while Guardiola will hope that resting French star Franck Ribery at the weekend has allowed him to recover fully from a sore ankle. Pilsen may be struggling to make an impression on the Champions League but they said on Monday they had won an important battle to retain the services of their coach Pavel Vrba, who has guided them to two titles since arriving in 2008. However, they are presently trailing leaders Sparta Prague by six points and have just one win from their last four games.