Sir Alex Ferguson will play Alan Smith in central midfield as a replacement for captain Roy Keane who has been rested for the trip to Budapest for the second-leg tie against Debrecen.

Three changes are expected, from the United side which beat Villa at the weekend with Mikael Silvestre and John O’Shea left at home as the Red Devils look to build on the 3-0 first-leg lead.

Wes Brown and Gabriel Heinze will make their first appearances of the campaign in a reshuffled defence. Ferguson has stated Cristiano Ronaldo and Ryan Giggs will get a game, leaving Ruud van Nistelrooy and Wayne Rooney to battle it out for the last place in a three-man attacking formation.

Everton travel to Spain looking to overturn the 2-1 first-leg defeat to Villarreal with manager David Moyes hoping injuries to two of his strikers clear up.

Marcus Bent and James Beattie both travelled despite knee, ankle problems and a toe injury respectively. Lee Carsley, Gary Naysmith, Per Kroldrup are ruled out. Full-back Alessandro Pistone will be out for some time after damaging knee ligaments at the weekend.

Villarreal manager Manuel Pellegrini has a full squad available as he aims to send the club into the Champions League group stages for the first time ever.

Inter will play behind closed doors as they host Shakhtar Donetsk in tonight’s Champions League third round qualifier second-leg. It will be the first of four matches without supporters as they serve the punishment given by UEFA following violence against rivals Milan last season in the quarter-finals.

The Serie A giants go into the clash at the San Siro with a 2-0 advantage following goals from Adriano and Obafemi Martins in their impressive first leg victory in Ukraine.

Argentinian midfielder Juan Sebastian Veron, influential striker Adriano and defender Marco Materazzi could be rested as coach Roberto Mancini prepares for the start of the Italian league this weekend. New signings David Pizarro, Julio Cesar and Walter Samuel are set to feature.

Ajax take on Brondby knowing they cant afford a repeat of the mistakes made in the first leg against the Danish side as the Dutch giants twice threw away the lead during the 2-2 draw in Denmark.

Ajax coach Danny Blind will give a late fitness test to midfielder Nigel de Jong ahead of the crucial Champions League qualifying clash at the Amsterdam ArenA. Czech Republic midfielder Tomas Galasek is another doubt for Blind’s side but is excepted to feature. Brondby are coached by former Ajax and Denmark star Michael Laudrup, who could prevent his former side reaching the group stages.

Fixtures – 1st leg results in brackets
Club Brugge v Valerenga (0-1)
Rangers v Anorthosis (2-1)
Debrecen v Man. United (0-3)
Villarreal v Everton (2-1)
Slavia v Anderlecht (1-2)
Ajax v Brondby (2-2)
Bremen v Basel (1-2)
Internazionale v Shakhtar (2-0)