The Owls have returned to the second tier after a dramatic League One play-off campaign which saw them triumph against Barnsley at Wembley.
Darren Moore was sacked despite achieving promotion and new manager Xisco Munoz has a tough start to life in Yorkshire as they face relegated Saints.
After finishing bottom of the Premier League last campaign, an exodus was expected on the South Coast, however, James Ward-Prowse still remains at the club.
And despite bids from West Ham, the captain is expected to lead his side out for their first competitive game under new boss Russell Martin as they aim to bounce straight back to the top-flight.
Sheffield Wednesday vs Southampton: How to follow
This Championship clash will take place on Friday, August 4.
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Kick-off at Hillsborough is scheduled for 8pm.
talkSPORT will have live and EXCLUSIVE coverage of the game presented by Adrian Durham.
Commentary will come from Sam Matterface, former Chelsea defender Scott Minto and ex-Ipswich manager Mick McCarthy.
To tune in to talkSPORT or talkSPORT 2 through the website, click HERE for the live stream.
You can also listen via the talkSPORT app, on DAB digital radio, through your smart speaker and on 1089 or 1053 AM.
Sheffield Wednesday vs Southampton: Team news
New Wednesday manager Munoz's first line-up could include some fresh faces with Pol Valentin, Juan Delgado, Di'Shon Bernard and Ashley Fletcher arriving at the club this summer.
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They could all feature alongside main men Barry Bannan and Josh Windass who starred in the Owls' League One play-off winning campaign.
As for Southampton, they could have a very strong line-up on show, having retained Ward-Prowse and Romeo Lavia throughout the transfer window so far.
New arrivals Shea Charles and Ryan Manning are likely to start for the Saints who sold Mohamed Salisu to Monaco this week.
Sheffield Wednesday vs Southampton: What has been said?
Southampton boss Martin is keen for his players to move on from the feeling of relegation as they gear up for the season opener.
He said: "We have a bit too much disappointment at times, still, which is not going to change overnight when you've had the season the club's had last season.
"The job we have as a coaching staff is to make sure that changes quickly, because we want to win - we want to win a lot - and we want to make sure that's the demand from everyone of each other.
"That's not an overnight thing, but I think the lads are enjoying what they're doing on the pitch and that's going to help a lot."
Sheffield Wednesday vs Southampton: Match facts
New Sheffield Wednesday manager Xisco Munoz led Watford to promotion from the Championship in the 2020-21 campaign, winning 18 of 26 league games after taking over in December (D3 L5). On home soil, he won 12 out of 13 Championship matches that season, losing the other to QPR.
Southampton have failed to win their opening league fixture to a season in each of the last nine campaigns (D4 L5 - all in the Premier League), since beating West Brom 1-0 away from home on MD1 in 2013-14. Indeed, the Saints have lost their season opener in each of the last four campaigns.
Sheffield Wednesday lost just one of their 23 home league games last term (W16 D6), the joint-fewest defeats across the top four tiers in 2022-23. They are currently unbeaten in 19 games at Hillsborough (W14 D5), last going longer without defeat on home soil between February 1980 - January 1981 (23).
Sheffield Wednesday are winless in their last four games against Southampton in all competitions (D1 L3) since a 2-0 win in the Championship in April 2009. The two sides did play out a 1-1 draw in the League Cup last season, with the Saints eventually progressing 6-5 on penalties.
This will be the first league meeting between Sheffield Wednesday and Southampton since the 2010-11 League One campaign, with the Saints doing the league double over the Owls that season.