Chelsea, Inter Milan and Bayern Munich are looking to the Champions League to help relieve growing domestic pressures but face tricky away tasks in their first-leg matches in the last 16.
Of the big guns who had been expected to go through when the draw was made, only Real Madrid are in the best frame of mind for their visit to CSKA Moscow.
Chelsea go to Napoli with manager Andre Villas-Boas under fire and with a team that appear to have lost their confidence amid reports of a mini-mutiny from players last week.
The Serie A side, which beat Manchester City at home in the group phase, are also hitting form, beating Fiorentina 3-0 Friday.
Villas-Boas is thought likely to drop Fernando Torres, who failed to score while Didier Drogba was away on Africa Cup of Nations duty.
Drogba could be recalled along with midfielder Frank Lampard, and defender Ashley Cole is in contention after injury but central defender John Terry is still a major doubt because of a knee problem.
“It is a 50-50 chance. To give you an idea he trained 100 per cent two days ago but the day after he couldn’t train, ” Villas-Boas said of Terry.
If Terry does not make it, Villas-Boas said he felt his side still had enough experience and strength to put in a good performance.
“If he misses out on Tuesday, then we will miss a top player who gives us great defensive stability,” he said.
“It would be a massive loss for us, and I will leave it as late as possible and make a decision on him after training in Naples.
“But I think there is still enough emotion (in the team) without him.”
Napoli coach Walter Mazzarri will have to watch from the stands of the San Paolo stadium as he serves a touchline ban for having jostled Villarreal’s Nilmar in the group phase.
Mazzarri can count on the good form of Uruguayan striker Edinson Cavani, who has scored three goals in his last two Serie A outings for a tally of 15, plus four notched in Europe.
Mazzarri has, however, potential trouble in defence with the likely absence of Argentine Hugo Campagnaro.
“I do not know if (Campagnaro) can make it,” Mazzarri said.
“Gianluca Grava is the ideal man to replace him. He has experience and quality.”
Inter Milan, the 2010 Champions League winners, would have been favourites to beat Marseille, but three straight defeats in the Serie A with a 0-8 goal difference give an idea of their present troubles.
A debacle in France on Wednesday could be fatal to coach Claudio Ranieri, leading to a second firing in a season that the Nerazzurri began under Gian Piero Gasperini.
Marseille striker Loic Remy has, meanwhile, been ruled out of the game with a hamstring injury.
Real Madrid landed in chilly Moscow on Sunday night in good spirits for Tuesday’s match against CSKA – but without injured winger Angel di Maria, who suffered a sprained knee in Saturday’s 4-0 destruction of Racing Santander.
Jose Mourinho’s team are in good heart after winning their last eight games in La Liga, on a flood of goals. They have opened up a massive 10-point lead over world champions Barcelona.
Basel will be outsiders against Bayern Munich on Wednesday in a special match for the Swiss club’s coach, Heiko Vogel, who was a youth team coach at Bayern from 1998 to 2007 and knows a number of the current senior squad well.
However Bayern have lost their early-season form and have slipped to third in the table after a goalless draw at bottom side Freiburg on Saturday, leaving them four points off leaders Borussia Dortmund.
