While the Premier League new boys are tuning up for their top-flight return, their Italian visitors are still adjusting to life under new management.
Match preview
Bouncing back to the Premier League at the first time of asking, Southampton finished fourth in the Championship last season after an uneven campaign that featured both a worryingly slow start and an excellent 25-game unbeaten streak.
Seeing off West Bromwich Albion in the playoff semi-finals set up a Wembley meeting with Leeds United, in which Adam Armstrong's 24th-minute strike secured the south coast club's return to England's top flight.
Head coach Russell Martin was the architect of their success, though his priority in the Premier League may be improving a defence that ranked only 14th for goals conceded in the second tier last term.
With one eye on the tough challenge ahead, Southampton have played several friendlies so far this summer, winning all but one - a 2-0 reverse to Oxford United. Martin's men had beaten Eastleigh 7-1, Bordeaux 3-2 and Montpellier 3-1, before putting Millwall to the sword last week.
Ahead of a daunting trip to St James' Park, where Newcastle United await on the Premier League's first weekend, Saints face two more pre-season tests, and Wednesday's game against Lazio will be followed by a final run-out at home to Getafe.
After a tumultuous 2023-24 season, which saw Maurizio Sarri quit mid-season before replacement Igor Tudor followed him through the door a few months later, Lazio are aiming to get back on an even keel ahead of the upcoming campaign.
Far from a popular appointment with the Biancocelesti's fans, ex-Hellas Verona coach Marco Baroni is the new man in charge, as the Rome club begin life without former talisman Ciro Immobile.
Following an injury-scarred year, the Italy striker was left out of Luciano Spalletti's squad for Euro 2024, and he subsequently left Stadio Olimpico for Turkish giants Besiktas.
Helping to further balance the books, big earners such as Luis Alberto and Felipe Anderson have also departed, as Baroni starts the process of revitalising a squad that finished runners-up in Serie A just over a year ago but then stumbled into seventh last term.
So far in pre-season, Lazio have defeated Trapani, Hansa Rostock and Frosinone, only faltering in a 1-1 draw with Triestina; and after visiting England, they will then meet Cadiz, before hosting newly-promoted Venezia on Serie A's opening matchday.
Southampton friendly form:
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Lazio friendly form:
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Team News
Though Scotland striker Che Adams recently left Southampton for Torino, Wednesday's hosts have since completed the signing of Ben Brereton Diaz, who scored six goals in 14 Premier League games on loan at struggling Sheffield United last season.
In the recent friendly against Millwall, Russell Martin fielded a flexible 3-5-2 formation, with Adam Armstrong and Samuel Edozie leading the attack, but Brereton Diaz could now add more presence up front.
Elsewhere, Adam Lallana - back at the club after a decade - should feature at some stage, while new boy Yukinari Sugawara has impressed so far and is set to start at right back. It remains to be seen whether Kamaldeen Sulemana and Sekou Mara can overcome injuries in time to play.
Meanwhile, Lazio's front line will be led by Taty Castellanos, who is now seeking to assert himself as the Biancocelesti's main marksman following Ciro Immobile's emotional exit.
The Argentinian striker only found the net four times in Serie A during his first year at the club, but after scoring in last month's 3-0 win over Hansa Rostock he will join new captain Mattia Zaccagni in the visitors' attack.
New signings Fisayo Dele-Bashiru, Loum Tchaouna and Tijjani Noslin - the latter of whom was with Marco Baroni at Verona last season - all featured against Frosinone last time out and should do so again at St Mary's.
Southampton possible starting lineup:
McCarthy; Edwards, Stevens, Harwood-Bellis; Sugawara, Aribo, Downes, Smallbone, Taylor; Armstrong, Brereton Diaz
Lazio possible starting lineup:
Provedel; Lazzari, Casale, Patric, Pellegrini; Cataldi, Guendouzi; Tchaouna, Noslin, Zaccagni; Castellanos