Defender Dejan Lovren's second-half header was enough for the Saints to leave Merseyside with all three points and leave Liverpool fans cursing their side's lack of penetration in the final third.
Brendan Rodgers' men—as they have done so often this season—started well and almost took the lead through a Steven Gerrard free kick that goalkeeper Artur Boruc did well to turn over at full stretch.
There were claims for a penalty when Lovren sent Daniel Sturridge tumbling in the area but referee Neil Swarbrick waved play on.
Victor Moses—making his home debut—also went close to opening the scoring but the Reds failed to turn their early dominance into goals and, as has been the case in each of their previous four league games, fired a second-half blank.
Read on to to discover five things that became apparent during Saturday's encounter.
Forward Iago Aspas has looked largely ineffective since his move to Anfield from Celta Vigo during the summer and showed no signs of an upturn in form during Saturday's defeat.
There have been glimpses of skill and trickery during his first few outings as a Liverpool player but nothing to justify the £7.5 million fee that the Daily Mail reports Rodgers shelled out to acquire his services.
The Spaniard at times looked out of his depth as the Reds struggled to break down a sturdy Southampton defence.
He was knocked off the ball far too easily, was guilty of many a misplaced pass and struggled to retain possession. In fact, at times his first touch was that bad that his second touch became a tackle.
Being hauled off and replaced by Raheem Sterling at half-time more or less summed up life at Anfield for Aspas at the moment.
Rodgers has been quick to leap to the forward's defence, but James Pearce of the Liverpool Echo reports that Aspas has already been put on a special weight-training programme to help him deal with the physical demands of Premier League football.
He should—as should all new signings—be afforded time to settle and get to grips with English football, but the signs were without doubt there on Saturday that Aspas has work to do if he is to avoid becoming another Fabio Borini-type story.
Liverpool's teamsheet may have raised an eyebrow or two when recognised centre-backs Kolo Toure and Mamadou Sakho were selected to fill the right-back and left-back roles, respectively.
Rodgers decided on Martin Skrtel and the fit-again Daniel Agger to occupy the two central-defensive positions yet opted for Toure and Sakho at full-back, despite naming Martin Kelly, Andre Wisdom and Jose Enrique amongst the substitutes.
Toure has been impressive since his switch from Manchester City but looked uncomfortable when ousted from his natural position.
He was on more than one occasion caught in possession and it was his mistimed clearance from a Southampton throw-in that gifted the Saints the corner from which Lovren headed home.
By choosing not to deploy any recognised full-backs, Rodgers side appeared unable to demonstrate the style of football he has worked so tirelessly to implement.
The "play the ball out from the back" method that has at times this season looked very effective was noticeable by its absence as both Toure and Sakho failed to go wide when goalkeeper Simon Mignolet was looking for options.
The Reds caused themselves numerous problems by repeatedly surrendering possession in their own half and as a result found themselves on the back foot.
Wisdom, admittedly did not have the best of games during the 2-2 draw with Swansea yet still appears a more reliable option than Toure at right-back. That is not taking anything away from the Ivorian's ability in his favoured centre-back position.
Jose Enrique, on the other hand, must have wondered what he had done wrong. The Spaniard has been both defensively and offensively sound during the Reds' winning start to the new season yet found himself ousted to incorporate Sakho.
To ensure his side maintain their positive start Rodgers needs to pick his best team and not just his best 11 players—meaning unless ravaged by injuries, only two from Skrtel, Agger, Toure and Sakho should start.
Philippe Coutinho has been nothing short of sensational since his January move from Inter Milan.
So, Liverpool fans all over the world would have winced as one when the little Brazilian landed awkwardly following a challenge from Ashley Williams during the 2-2 draw away at Swansea on the 16th.
Their worst fears were confirmed when Coutinho was ruled out until the end of October with a shoulder injury that would require surgery.
Following his withdrawal at the Liberty Stadium the Reds immediately lacked creativity and imagination. They were impotent in attack and Swansea from thereon in dominated possession and looked the most likely team to snatch a win.
The second-half performance at Swansea appeared to carry over to the weekend with the Coutinho's absence heavily felt as the Reds appeared short of ideas in the final third.
The skill, vision and ability to deliver that all-important eye of a needle pass was noticeable by its absence as Rodgers' side chased a game that—if they have serious intentions of breaking into the top four—should be winning.
Fans will be hoping that their club's failure to capture at least one of reported summer targets Willian, Henrikh Mkhitaryan and Diego Costa, as reported by Sky Sports, the Mirror and the BBC respectively, does not come back to haunt them.
Simon Mignolet had big shoes to fill when he replaced Pepe Reina as Liverpool's first-choice goalkeeper during the summer.
The Spaniard broke record after record during his eight-year stint at Anfield and was as popular with his teammates as he was with the fans.
It was a bold move to replace such an established club figure with a man six years his junior but a move that has paid off during the opening weeks of the season.
Mignolet has rescued points for his side in each and every game he has played whether it be saves late in matches to maintain a lead, to preserve a draw when hanging on in a game or to keep his side in with a shout when trailing.
Penalty saves, world-class saves and triple saves. We've seen them all already in his short Liverpool career.
It was the aforementioned triple save during Saturday's defeat that kept the Reds in with a chance of rescuing a point as the game wore on.
Lackadaisical Liverpool defending gifted Southampton the chance to extend their lead and kill the game off but a save from defender Luke Shaw followed by a point-blank save to prevent a Sakho own goal and then an athletic punch to prevent Steven Davis tapping in somehow kept the score at just one.
Although almost losing possession on the edge of his penalty area led to more comical Reds defending he was arguably the only player in a Liverpool shirt to come out of the game with any credit.
Although the Reds have a very good win/loss record since Suarez's ban for the infamous bite on Branislav Ivanovic, the striker's return could not come at a better time for the Reds.
Although they have won three out of five league games this season, their tally of just five goals in those five games and their failure to score a goal in the second half of a game is worrying.
Daniel Sturridge has been a revelation in his absence, scoring in each of his first four league games; however the thigh injury that kept him out of England's recent fixtures may just well be catching up with him.
With Rodgers allowing both Andy Carroll and Borini (loan) to depart Anfield this summer and Aspas appearing to be preferred out wide, Sturridge has been the only recognised striker available for selection so far.
While he has carried the goal burden ever so well, it appears that if Sturridge doesn't score then at the moment, neither do Liverpool.
Against Southampton they were toothless (no pun intended) in attack, Sturridge had an off day and Aspas was never in the game.
The Reds mustered 10 shots on goal (via BBC) but only really threatened with a couple of Steven Gerrard free-kicks that were turned away by Boruc.
They were crying out for Suarez.
What better fixture to come back into than Manchester United away. The feisty Uruguayan will relish the red-hot atmosphere of Old Trafford and wouldn't it be just like him to pop up with a goal.
With Liverpool showing their first signs of stuttering, the return of Suarez will no doubt give everyone at the club a real boost going into what on paper looks like a winnable run of fixtures.