Both sides have made movements in the transfer window, and this will be an opportunity for managers Frank Lampard and Mark Hughes to get the new recruits valuable playing time under their belts.
Derby have so far signed Florian Jozefzoon from Brentford (£2.8m) as well as completing the loan signings of hot prospects Harry Wilson (Liverpool) and Mason Mount (Chelsea).
Southampton have been busy since the window opened, signing Stuart Armstrong (Celtic - £7m), Mohamed Elyounoussi (Basel - £16m), Angus Gunn (Manchester City - £10m) and Jannik Vestergaard (Gladbach - £20m).
Derby fell to a defeat in their last friendly against Mansfield Town on Wednesday, losing 3-1 at the One Call Stadium.
Southampton haven't been in action since last Wednesday when they emerged victorious in a 3-2 win against Jiangsu Suning in China.
Both sides desperate to improve on last season
With no Derby players travelling to Russia's incredible World Cup and just three Southampton players making the journey, this game will see both sides at full strength as they build fitness and seek to improve on last season's mediocre finishes.
Derby were beaten 2-1 on aggregate in the Championship play-off semi-finals against eventual winners Fulham, and Southampton were lucky to avoid the jaws of Premier League relegation with late wins against Bournemouth and Swansea.
Both sides have appointed new managers in the off-season, each making their own signings in order to do things 'their way'.
Lampard will be looking to hit the ground running in his first competitive game in management against Reading in August, whereas Hughes will be vying to lead the Saints ship to safety yet again, after succeeding on a short-term deal last season.
New attacking era for Saints?
With Dusan Tadic leaving for Ajax, Southampton have been forced to reinvent themselves in attacking play - aided by the signings of Armstrong and Elyounoussi.
Nathan Redmond looks to be a vital part of the Saints attack and looked at his best last week against Jiangsu Suning, utilizing his pace and direct running and even grabbing a goal.
There will be a battle between Charlie Austin and Manolo Gabbiadini for the main striker berth, with most fans suggesting that there isn't much between the two, despite their clear differences in play style.
They combined famously on that special night in Swansea, with Austin's blocked shot falling straight to the feet of the charismatic Italian, who slotted home to effectively seal Saints' survival.