Adrian Clarke looks at key tactical points in Matchweek 20.
Ralph Hasenhuttl has set his side up in a 4-4-2 formation and created an impressive off-the-ball structure.
Their defensive solidity was highlighted on Saturday, when Southampton beat the Gunners 1-0 at home in the FA Cup.
The stability of Southampton's backline has been key to a number of their performances.
This lack of rotation has helped them strike up an impressive connection.
Indeed, Southampton have the least-changed defence in the top flight at this halfway stage of the season.
But with Walker-Peters and Bertrand ruled out of Tuesday's match through injury and suspension respectively, Southampton's defence will have to adapt.
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However, Southampton’s solidity is spread throughout their team and is not solely left to the defence.
To put that into some kind of context, Dani Ceballos has won the most tackles for Arsenal this season, with 16.
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Apart from the 5-2 defeat to Spurs and a 3-2 turnaround loss to Man Utd, Southampton have been very solid at home.
They have conceded only nine times at St Mary’s, the joint-third best record in the Premier League, behind only Man City and Burnley.
Southampton have also faced the second-fewest number of shots on target in home contests, with 27.
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Ever-present Bednarek will likely be tasked with marking Alexandre Lacazette in a duel worth keeping a close eye on.
Bednarek has been extremely assured throughout this season, starring alongside Stephens and Vestergaard.
The statistics show the Pole is one of the best central defenders in the league, so it was no surprise to see him tied down to a new long-term contract last month.
With the robust Bednarek at the heart of their defence, Southampton know Arsenal will have a tough time trying to catch them off guard, even without their two first-choice full-backs.