Southampton were originally due to take on Shrewsbury in the third round on January 9, but the match had to be rearranged after a coronavirus outbreak at the League One club; the fixture finally took place on Tuesday night, and it was a straightforward 2-0 success for Ralph Hasenhuttl's side.
The Saints have only won the FA Cup on one previous occasion, lifting the trophy in 1976 courtesy of a famous victory over Manchester United, with Bobby Stokes netting the only goal of the contest.
Hasenhuttl's team will enter this game off the back of successive home victories, including a 1-0 win over Liverpool in the Premier League at the start of the month, and an excellent 2020-21 campaign to date has left the club in ninth spot in the table ahead of their next league game on January 26, which is also against Arsenal.
The Gunners were far from at their best in the third round against Newcastle, but Emile Smith Rowe and Pierre-Emerick Aubameyang both scored in extra time to secure a 2-0 victory for the FA Cup holders.
Mikel Arteta's side have taken four points from their two league matches since then, including a dominant 3-0 win over Newcastle on Monday evening to move into 10th spot in the table, two points behind Southampton.
Arsenal have won this competition on 14 occasions and are the holders, beating Chelsea 2-1 at Wembley courtesy of a brace from Aubameyang, and it might again represent the team's best chance of silverware this term despite their involvement in the Europa League.
It is almost two years since the capital giants last lost an FA Cup fixture, while they are unbeaten in their last four matches with Southampton since a 3-2 defeat at St Mary's in December 2018.
The two teams played out a 1-1 draw in the Premier League just over a month ago, though, and it is difficult to know what to expect in this match as both managers could spring surprises with their team selections.
Southampton FA Cup form: DLWDLW
Southampton form (all competitions): LDDWLW
Arsenal FA Cup form: WWWWWW
Arsenal form (all competitions): WWWWDW
However, the Saints are set to be boosted by the return of Danny Ings, who has served his isolation period following a positive coronavirus test, and the striker should be in the XI on Saturday.
Southampton possible starting lineup:
Forster; Walker-Peters, Bednarek, Stephens, Bertrand; Armstrong, Diallo, Ward-Prowse, Walcott; Ings, Adams
Arsenal possible starting lineup:
Leno; Bellerin, Holding, Gabriel, Tierney; Elneny, Partey; Pepe, Willian, Martinelli; Aubameyang
We say: Southampton 2-1 Arsenal
Arsenal's recent form and history in the FA Cup must be respected, but Southampton have been excellent for much of the campaign. Hasenhuttl is likely to select a strong XI for this weekend's contest, and we fancy the Saints to edge a tight encounter, eliminating the hosts in the process, to set up a fifth-round clash with either Chorley or Wolverhampton Wanderers.