The Gunners currently top the division on 51 points and with nearest challengers Manchester City and Chelsea not playing until Wednesday, Arsene Wenger's side could open up a healthy gap with three points against the Saints at St Mary's.
The home side enter the match having lost just one of their last five matches in all competitions, but their league form has dipped following a strong start to the campaign. As it stands, they sit in ninth position in the table on 31 points.
Five of their eight league victories this season have come on their own patch, but they welcome an Arsenal team who have won eight of their 11 away fixtures in the league this season.
The corresponding match last season ended in a 1-1 draw, but Arsenal picked up all three points with a 2-0 win when the pair met at the Emirates Stadium earlier in the 2013-14 campaign.
The home side will be without Dejan Lovren and Gaston Ramirez, who both suffered ankle injuries against Sunderland last time out, while summer signing Pablo Osvaldo has been suspended following a training-ground incident with club captain Jose Fonte.
Arsenal will be without the services of Aaron Ramsey through injury, while Mikel Artera is also a doubt having just returned to training this week.
Possible starting lineups
Southampton: Boruc; Chambers, Fonte, Yoshida, Shaw; Schneiderlin, Davis, Cork; Lallana, Rodriguez, Lambert
Arsenal: Szczesny; Sagna, Mertesacker, Koscielny, Gibbs; Wilshere, Flamini; Cazorla, Ozil, Podolski; Giroud
Sports Mole says: 1-2