The Magpies moved into the top four with their victory over Stoke City last week, and Brighton will be eager to ensure they don’t climb even further as they look to exact revenge following the dramatic turnaround in the Championship title race last season.
The Seagulls were in pole position to claim the title but a late defeat on the final day at Aston Villa, combined with Newcastle's home win over Barnsley, meant the Magpies stole the crown.
Rafael Benítez will no doubt see it as another winnable game as United look to establish themselves as top-half contenders.
Newcastle will be without Florian Lejeune for their trip to the south coast after the defender picked up a knock to the same ankle which ruled him out of four of United’s first five games.
Meanwhile, goalkeeper Karl Darlow is expected to make his return to the squad and replace Freddie Woodman on the bench.
Aleksander Mitrović will serve the last of his three-game ban for the violent conduct charge picked up after the game against West Ham.
Massadio Haidara and Paul Dummett also remain sidelined for the visitors.
The visitors are expected to start the game with the same back four and middle as their last game while Christian Atsu and Ayoze Pérez are also expected to keep their places in the side after impressive performances last time out.
The hosts welcome back Glenn Murray, Gaetan Bong and Izzy Brown from injury, while Sam Baldock, Steve Sidwell and Beram Kayal will all miss out.
United come into the game on the back of three successive wins. A 2-1 victory over Stoke City last time out put the Magpies into the top four.
The Seagulls picked up their first win two weeks ago with an impressive 3-1 victory over West Bromwich Albion.
They lost their most recent Premier League game at Bournemouth however, losing 2-1, and followed it up with another loss to The Cherries in the Carabao Cup on Tuesday.
The Magpies won both league meetings last season winning 2-0 at home before a 2-1 victory at the AMEX Stadium in February.
Brighton have eliminated their Tyneside opponents from the FA Cup twice in their only other two meetings since the turn of the century.
A 1-0 victory for the Seagulls in 2012 was followed up by a 2-0 win a year later.