With absentees in the double figures just three days on from a gruelling 120-minute EFL Cup final against Chelsea, the Reds boss unsurprisingly drafted a few inexperienced academy products into his first XI for the visit of the Saints.
Bobby Clark, James McConnell and Lewis Koumas were all given the nod from the first whistle, while Jayden Danns, Trey Nyoni, Kaide Gordon, Calum Scanlon and Amara Nallo all occupied places on the bench.
The hosts' decimated team came under the cosh against their Championship foes on several occasions, but Caoimhin Kelleher stood tall in the first half, where Koumas opened the scoring with his first senior goal.
On his maiden first-team appearance for the Reds, Koumas - son of former Liverpool youngster and Wales international Jason Koumas - darted infield, let fly from inside the D and saw his low strike deceive Joe Lumley thanks to a deflection off of Jan Bednarek's leg.
Southampton let a couple more promising openings pass them by in the second half, in which Koumas's fellow 18-year-old Danns came off the bench to double Liverpool's lead with a delicate chip over Lumley in front of the Kop.
Just 15 minutes later, Danns capped off a magical evening with his second and Liverpool's third, showcasing exceptional predatory instincts to lash home the rebound after Conor Bradley's effort was saved by Lumley.
The three-goal beating of the Saints marked the first time in Liverpool's history that two players aged 18 or under have scored in one senior game, but Klopp has implored journalists not to pile the pressure or set unrealistic expectations on the young duo.
"I understand 100 per cent but it's a little bit like with the new darts sensation," Klopp told the media, referencing 17-year-old Littler's rise to prominence on the darts scene after his runners-up finish at the PDC World Darts Championship.
"It's fine for tonight, absolutely, but from tomorrow on leave the boys in the corner please and don't ask where are they now, where are they now, where are they now. They have a lot to improve, a lot to learn.
"They will have their moments and in the moment, with our squad situation, they will have more moments than they ever have expected probably, so that's one thing. The other is they're exceptional talents."
Speaking to ITV Sport on the Anfield turf, Danns - whose father Neil Danns was a Guyana international - admitted that he would struggle to sleep after fulfilling his dream of scoring in front of the Kop end.
"It's a dream come true," the teenage striker said. "I've supported the club since I was young, since birth, so to come on and score at the Kop end - it's unreal. It doesn't feel real to me. It feels like I'm in a movie. I don't think I'll sleep tonight.
"Obviously it was [Harvey Elliott] who slipped me in. I've just seen him and I thought he's got the vision to make it. The goalkeeper came close and when he comes that close you have to dink it. The second one was just pure joy. I didn't think it would come to me. I was happy with one but when two came I just went sliding [and] as you've seen, I lost all composure!"
Liverpool have been drawn against long-time nemesis Manchester United in the quarter-finals of the FA Cup and now turn their attention back to Premier League matters, facing Nottingham Forest -whom the Red Devils beat 1-0 in their fifth-round tie - at the City Ground on Saturday afternoon.