Last season's League One champions and relegated Premier League outfit have accumulated four points from their opening two fixtures in the new second tier.
Match preview
Given the frequent speculation regarding some of the club's key players, newly-appointed head coach Russell Martin has needed to be realistic about Southampton's start to the season.
Nevertheless, that will not have stopped him aiming high, and accumulating four points from fixtures against Sheffield Wednesday and Norwich City can be deemed to be a positive return.
That is particularly the case when they found themselves behind to the Canaries on three occasions last weekend, eventually sealing a share of the spoils through a last-gasp penalty.
With Romeo Lavia joining James Ward-Prowse in heading out of St Mary's, Martin will hope that he receives a portion of the funds that have been generated to add another figure to his engine room.
Depending on how they fare against their fellow South-coast side, he may feel that they require more than just out-and-out alternatives in midfield to keep pace in this division.
Even though Plymouth have made some shrewd additions during the summer transfer window, it was unclear how they would bed in and improve a side that won League One last season.
Steven Schumacher can only have been left delighted with his team's efforts thus far, four points coming from meetings with Huddersfield Town and Watford.
The clean sheet kept at Vicarage Road will have impressed him as much as the preceding 3-1 triumph over Huddersfield, and the foundations have been laid for a campaign without relegation issues.
However, Schumacher will stress to his squad that they cannot get ahead of themselves at this early stage, the Pilgrims needing to capitalise while momentum is on an upward curve.
These two teams have not met in a competitive fixture since Southampton posted a 3-1 success away from home at the back end of the 2010-11 League One season.
Plymouth Argyle Championship form:
W
D
Plymouth Argyle form (all competitions):
Southampton Championship form:
W
D
Southampton form (all competitions):
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Team News
Kaine Kesler-Hayden could return to the Plymouth XI after a foot injury, taking the spot of Saxon Earley at left-back.
While Luke Cundle and Finn Azaz are both options in the centre of the pitch, Schumacher may opt to keep the remainder of the side that impressed at Watford.
With Will Smallbone suffering an ankle injury last weekend, Martin may hand an opportunity to Shea Charles in central midfield.
Samuel Edozie is also a doubt due to the hamstring issue that he sustained versus Norwich, and whether Che Adams replaces him will depend on if there are any developments with his future.
The same applies with Nathan Tella, who is attracting interest from Germany, and Moussa Djenepo could be drafted into the team if required.
Plymouth Argyle possible starting lineup:
Hazard; Edwards, Scarr, Gibson, Earley; Wright, Houghton, Randell; Whittaker, Hardie, Mumba
Southampton possible starting lineup:
Bazunu; Walker-Peters, Bednarek, Stephens, Manning; Alcaraz, Charles, S.Armstrong; Tella, Adams, A.Armstrong
We say: Plymouth Argyle 2-2 Southampton
This has all the makings of a thrilling contest, Plymouth playing with the confidence that comes with having made a fast start and Southampton seeing goals scored at both ends of the pitch. It leaves us to predict a high-scoring draw, one which will suit the home side more so than the visitors.