Manager Alex Ferguson will hope his Red Devils will get off to a firing start thanks to his lethal striker force including former Toffees forward Wayne Rooney.
New signing Shinji Kagawa is likely to start behind Rooney and Van Persie while Fergie will be pleased with the return of captain Nemanja Vidic who will partner veteran Rio Ferdinand at the heart of defence.
Everton boss David Moyes hopes midfielder Mourane Fellaini is fit while Phil Neville will replace former United man Darren Gibson in the holding role. Former Rangers man Steven Naismith could start ahead of Seamus Coleman at right wing.
Goalkeeper Tim Howard will make his 184th consecutive appearance for the Toffees. The Blues will eye their fourth home victory in 21 meetings against the Red Devils.
Ferguson will be confused whether to start winger Nani or Ashley Young while striker Danny Welbeck is the third choice and behind him is Mexican forward Javier Hernandez.
United are favourites to clinch three points but the Toffees have created many shock moves in the past.
Trivia: Both teams have met 181 times with 64 wins for Everton and 81 for United.
Everton are unbeaten in last nine games of the last season. The Blues came back to draw 4-4 last time around.
Everton (4-2-3-1): Howard-Hibbert, Heitinga, Jagielka, Baines-Neville, Fellaini-Osman, Naismith, Pienaar-Jelavic.
Manchester United: (4-2-3-1): De Gea-Valencia, Ferdinand, Vidic, Evra-Carrick, Cleverly-Nani, Kagawa, Rooney-Van Persie.