Slavisa Jokanovic will be hoping for a positive start to his reign as Blades boss with promotion back to the Premier League being a firm objective for the Yorkshiremen.
Lee Bowyer's Blues will look to build on what was an entertaining and strong end to last season after they managed to beat the drop before it came down to the final day of the season.
• Team news
Aaron Ramsdale and Sander Berge look set to start for Sheffield United despite talks of them moving on in this transfer window.
Enda Stevens, Billy Sharp and Oli McBurnie are all struggling with fitness and are likely to miss out on this tie.
Neil Etheridge has been in hospital with COVID-19, which means Matija Sarkic should make his league debut in goal. Aside from that Bowyer has a fully fit squad to chose from.
• Predicted lineups
Sheffield United (4-3-3):
Ramsdale; Robinson, Egan, Basham, Baldock; Berge, Fleck, Norwood; Burke, McGoldrick, Mousset.
Birmingham City (4-4-2):
Sarkic; Colin, Roberts, Dean, Pedersen; Chong, Gardner, Woods, Sanchez; Jutkiewicz, Hogan.
• Ones to watch
David McGoldrick - Sheffield United
McGoldrick featured in 35 out of 38 Premier League games for the Blades last campaign and although it was not a season to remember, he still managed to get score eight goals and notch one assist.
At 33 years of age, McGoldrick is hugely experienced, and in his most recent Championship season, he struck 15 goals, averaging a goal every 216 minutes.
His desire to score goals along with his work rate off the ball and quality in possession certainly make him a player that the Birmingham defenders need to keep an eye on, as he has the ability to single-handedly win games - especially at Championship level.
32-year-old Jutkiewicz is another very experienced Championship player. In his last four seasons he has scored a combined total of 42 Championship goals.
Jutkiewicz enjoys a physical battle with defenders using his strength and power to his advantage. He has an excellent heading ability with five of his eight goals last season coming with his head.
The Blues number 10 has proved on many occasions he can be a real handful for defenders and it is important that Sheffield United keep close tabs on him because he has the knack of sniffing out goal-scoring opportunities.
• Previous meetings
The last time these two sides met, the game ended in a 1-1 draw. Enda Stevens opened the scoring for the Blades before Michael Morrison equalised just four minutes later.
Out of their last five meetings, Birmingham have won two and there has been three draws. The last time Birmingham beat Sheffield United was back in 2018 when Marc Roberts and Jacques Maghoma were on the scoresheet for the Blues.
The last time Sheffield United won this fixture was in 2009.
Last time out:
• Where to watch
The game kicks off at 20:00 BST on Saturday 7 August 2021.
The game will be broadcasted live on Sky Sports' Main event channel, their Football channel and it will also be available via Sky Go.
• What the managers have said
New Blades boss Jokanovic told Yorkshire Live just how much he was looking forward to playing in front of a full crowd at Bramall Lane:
"I have only been here one month and a few days working, but this will be really exciting and fantastic to be in front of 30,000 people.
"I am not wanting to start crying and looking at what is behind us, we have made the best job we could have made of the situation and I don't want to be looking for some excuse.
"I am ready, we are ready and I am looking forward to joining those Blades in the stands and that is it."