Both sides prevailed by 1-0 scorelines in midweek, with the Saints overcoming Bournemouth on the South Coast while the Gunners got the better of PSV Eindhoven in the Europa League.
Match preview
While a lot of the pre-match talk on social media centred around whether Bournemouth vs. Southampton can indeed be classed as a derby, Ralph Hasenhuttl's side did what they needed to do on the Vitality Stadium turf to end their dampening winless run.
Che Adams was on hand to meet Romain Perraud's inch-perfect cross and head home the opener with just nine minutes on the clock, and the Saints defence held firm for the remaining 81 minutes, although Mohammed Salisu was required to make a vital goal-line clearance in the second half.
Victory at the Vitality snapped a five-game winless run for Southampton, but Ralph Hasenhuttl undoubtedly remains a man under immense pressure, despite leading his side all the way up to 14th in the table, with a two-point gap now separating them from the relegation places.
Given the fact that Adams's header was only the third goal that Southampton have scored in their last 540 minutes of top-flight football, fan frustrations are understandable, and results not going Southampton's way this weekend could plunge them straight back into danger.
The Saints sent a stark warning to Big Six clubs when they beat Chelsea at St Mary's earlier this season, but Hasenhuttl's side have now gone seven top-flight games at home without a clean sheet, and not since February have they picked up back-to-back wins in the Premier League.
Perhaps paying homage to ex-captain Tony Adams's one-nil to the Arsenal performance on Strictly Come Dancing, Mikel Arteta's men have rediscovered their penchant for narrow wins in recent weeks, as their victory over PSV on Thursday represented their third triumph in a row by that scoreline.
It could and probably should have been more, but Granit Xhaka's half-volley was all it took for Arsenal to seal their place in the Europa League knockout stages following previous 1-0 wins over Bodo/Glimt and Leeds United - the latter of which was not without drama from the first whistle to the last.
By overcoming a power cut, seeing Patrick Bamford's penalty fly wide and escaping a red card in the dying embers, Arsenal have opened up a four-point gap at the top of the table ahead of the weekend's matches after recording their best-ever start to a Premier League season.
A spate of 1-0 victories may signal that fatigue from the relentless October schedule is starting to set in, but an eight-game winning streak says otherwise, and Arsenal travel to St Mary's having scored a league-high 10 and conceded a league-low three goals on the road this term.
However, St Mary's has traditionally not been a happy hunting ground for the Gunners, who lost 1-0 on the South Coast last term - their fifth defeat away to Southampton since January 2015 - but they did put three past Hasenhuttl's side without reply at the Emirates back in December.
Southampton Premier League form:
L
L
L
L
D
W
Arsenal Premier League form:
W
L
W
W
W
W
Arsenal form (all competitions):
W
W
W
W
W
W
Team News
Southampton were handed a concern when Kyle Walker-Peters limped off against Bournemouth in midweek, but the right-back was simply suffering from cramp and should be fine here. In contrast, Armel Bella-Kotchap (shoulder), Valentino Livramento (knee), and Romeo Lavia (thigh) are out.
Hasenhuttl will be forced into a change in midfield, with Ainsley Maitland-Niles unable to face his parent club, so Ibrahima Diallo can expect to get the nod alongside James Ward-Prowse in a bid to keep Arsenal quiet.
Centre-back Lyanco earned high praise for his performance off the bench against the Cherries as Hasenhuttl switched to a back five mid-game, but a four-man backline may still be preferred from the off as the Saints boss keeps faith with his midweek crop.
As for Arsenal, Bukayo Saka was a constant menace down the right-wing against PSV, but all he had to show for his efforts was a kick to the calf. The 21-year-old was moving gingerly towards the end of the match, but Arteta hopes he will quickly shake off the issue.
Mohamed Elneny (hamstring) and Emile Smith Rowe (groin) are out for months, and Oleksandr Zinchenko is also struggling to recover from a calf injury, which could therefore see Takehiro Tomiyasu hold the fort on the left-hand side again.
Gabriel Martinelli overcame an illness in time for Thursday's game and will be one of several regulars to return to the Arsenal XI here, with Aaron Ramsdale, Ben White, William Saliba and Thomas Partey also coming back in.
Southampton possible starting lineup:
Bazunu; Walker-Peters, Caleta-Car, Salisu, Perraud; Aribo, Diallo, Ward-Prowse, Elyounoussi; Adams, Armstrong
Arsenal possible starting lineup:
Ramsdale; White, Saliba, Gabriel, Tomiyasu; Xhaka, Partey; Saka, Odegaard, Martinelli; Jesus
We say: Southampton 0-2 Arsenal
Discontent is still alive at St Mary's even after their win over Bournemouth, who have been no pushovers in Gary O'Neil's tenure, and the pressure could weigh heavily on Hasenhuttl's shoulders again after Sunday's game.