The England striker has recovered from a hamstring injury and a positive Covid test to be recalled along with former Gunners forward Theo Walcott.
Che Adams also came into the side which shows six changes from their rescheduled third-round win over Shrewsbury in midweek. Fraser Forster, Jack Stephens, Jan Bednarek, James Ward-Prowse and Ibrahima Diallo all retained their places.
Arsenal made seven alterations from their 3-0 Premier League win over Newcastle on Monday night.
New signing Mat Ryan was named on the bench as Bernd Leno continued in goal, while Hector Bellerin and Gabriel Magalhaes came into the back four.
There were also starts for Mohamed Elneny, Nicolas Pepe, Willian, Gabriel Martinelli and Eddie Nketiah.
1*– Ward-Prowse just clanged the crossbar straight from a corner.
Arsenal have started slowly.
12* – Talking of which, Willian whips a cross into the area despite zero Arsenal players being in there. Southampton fail to clear and Cedric has a pop at goal, but it’s high and wide.
15* – Yeesh, a bit rusty from Gabriel. Adams has him on toast and steams past him and into the area for an atempt on goal, which Leno does well to save.
24* –GOAL Looks like that will go won as a Gabriel own goal. The holders have to wake up.
30* – Arsenal are on the ropes. Ings hits a smart volley at the back post, which Bellerin throws himself at to concede a corner, which comes to nothing.
37* – Willian and Pepe are not enjoying themselves this afternoon.
45* – Pepe gives away another needless free kick and Ward-Prowse has a sight of goal… but it’s a few yards wide.
48* – That’s your lot for the first half. Another goal for Southampton and it’ll be as good as over for Arsenal at this rate.
54* –Pepe is rolling about in agony after a late challenge from Bednarek. He looks to be OK though. That was a promising break for Arsenal, before the foul.
58* – Two good chances for Arsenal as Nketiah’s shot is first deflected wide before, from the corner, Holding scoops a shot over the bar after it drops for him.
66* – Better! Willian to Pepe to Nketiah, who skips inside and tries to bend a shot past Forster, but the keeper sticks out a boot.
70* – Third change for Arsenal as Lacazette replaces Bellerin.
83* – Nketiah takes advantage of confusion in the box for a shot at goal, but Ward-Prowse clears. Again, the flag is up as Pepe was earlier offside.
90* –Gabriel up top for the final few minutes! Desperate times…
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