Old Trafford plays host to Championship title holders.
Manchester United remain without long-term injury victims Owen Hargreaves and Anderson, with both midfielders absent with knee injuries.
Centre-back Rio Ferdinand is also out with a knee problem.
Newcastle striker Andy Carroll has been declared fit to lead the line, while former Red Devil Alan Smith is expected to shake off an ankle injury.
But Leon Best, Danny Simpson (both ankle), Steven Taylor (shoulder) and Dan Gosling (knee) will all miss out.
Injured: Anderson, Ferdinand, Hargreaves (all knee)
Doubtful: Smith (ankle)
Injured: Best & Simpson (both ankle), Gosling (knee), S Taylor (shoulder) (BBC Sport)
Chris Hughton would probably have preferred a less challenging opening Premier League fixture but his side goes into the match hoping his side can put in a performance that would go some way to proving his side have what it takes to avoid the drop and push on towards the top half of the table.
Sir Alex Ferguson has some key players out with injury but will hope that his side can continue their recent pre-season form to take all three points at Old Trafford. The Toon Army have not triumphed away to United in 38 years and it would take a brave man to bet on such an occurrence tonight.
Sir Alex Ferguson discusses injury concerns
Manchester United 6-0 Newcastle United January 2008
Newcastle United 5-0 Manchester United October 1996