In the opening round of this competition, United blanked Millwall 1-0, while the Saints scored twice in 16 minutes this weekend to defeat Leicester City 2-1 in Premier League action.
Match preview
After getting some payback against the Lions, who took them out in the second round of this tournament last year, Cambridge have an opportunity to reach the third stage for the first time since 1998/99.
Mark Bonner's side hold a 100% record so far at home on this current domestic campaign, conceding just once in their victories over MK Dons (1-0) and Exeter City (2-1).
Lately, they have had to fight their way from behind more often than not, but have reacted well when conceding, earning four points in their last three games, all matches in which they allowed the opening goal.
The second round of the EFL Cup has proven to be a challenging hurdle for Cambridge to clear, having made it to this point of the tournament in four consecutive seasons, losing the previous three by a combined score of 10-1.
Over the weekend, Bonner said they failed to sustain their own attacks or do enough to maintain possession as they suffered a ton of pressure in the opening half before coming back to draw Charlton Athletic 1-1.
Because of their poor starts of late, it has been more challenging for them to play the counter-attacking style that Bonner wants them to execute, though the U's boss has said he is pleased with how well his side have managed to dig themselves out of their deficits with some solid second-half performances.
Southampton reacted well on Saturday at King Power Stadium, as a second-half substitution made by manager Ralph Hasenhuttl sparked the Saints to their first road victory of the domestic campaign.
Known as "The Alpine Klopp", their Austrian manager has always employed some tactics which rely on a high tempo, with a heavy workload of pressing and rapid transitions.
They have been exposed and short at the back on multiple occasions this season, with the Saints conceding seven goals in only three EPL encounters thus far.
The Saints have only scored one first-half goal domestically on this current campaign, losing their only match domestically in which they tallied first, 4-1 to Tottenham, while they are unbeaten in league play when conceding the opener.
When out of possession, Southampton try to play with pressing triggers, while forcing their opponents to play a loose or long pass for their defenders to recover.
In addition to that, they are not afraid to be physical and give away cheap fouls to avoid being caught in transition, giving away 15 free kicks on Saturday against the Foxes.
Cambridge United EFL Cup form:
Cambridge United form (all competitions):
Southampton form (all competitions):
Team News
Liam O'Neil had the only goal in the first-round fixture for Cambridge against Millwall, Jack Lankester picked up an assist on the play and Will Mannion only had to make one save to collect the clean sheet.
Harvey Knibbs leads them with two goals domestically, notching the equaliser this weekend versus Charlton with Sam Smith assisting, while Smith and Joe Ironside have yet to score this season after tallying 15 and 14, respectively, over the previous domestic campaign.
There were four new faces in the U's starting 11 on Saturday as George Williams, Harrison Dunk, Adam May and James Brophy replaced Brandon Haunstrup, Jubril Okedina, O'Neil and Ironside.
A brace from Che Adams helped Southampton come back to beat Leicester on Saturday, his first two of the season, moving him ahead of Kyle Walker-Peters, James Ward-Prowse and Joe Aribo for first on the team.
Mohamed Elyounoussi led them with three goals in this competition last season, one more than Armando Broja, who is back at Chelsea after his loan spell with the Saints in 2021-22.
Tino Livramento is out with an ACL injury, while Romain Perraud will not be available until early next month due to a muscle issue.
Cambridge United possible starting lineup:
Mitov; Haunstrup, Okedina, Jones, Williams; Digby, O'Neil; Brophy, Knibbs, Smith; Ironside
Southampton possible starting lineup:
McCarthy; Djenepo, Bednarek, Lyanco, Valery; Lavia, Diallo; S. Armstrong, Elyounoussi, Walcott; Mara
We say: Cambridge United 0-3 Southampton
The Saints have not lost a second-round EFL Cup encounter away from home since 2005-06, when it was known as the Carling Cup, failing to concede on the road at this stage since 2013-14.
Cambridge have not fared well at this point of the tournament for a long time, and that was primarily against second or third-tier sides, so we do not expect them to trouble a Southampton team who had 12 different players score in the Premier League last season, while another eight had at least one assist.