Exeter City skipper Matt Taylor's thumping header helped the Grecians to a deserved point at St James' Park.
Taylor rose to meet Scott Golbourne's corner just after half time to cancel out Adam Lallana's opener.
Substitute Bertie Cozic came inches away from scoring a late winner but his curling effort was tipped onto the post by Kelvin Davis in stoppage time.
With Alex Russell and Marcus Stewart both picking up injuries at stadiummk last weekend the opportunity arose for Barry Corr and Joe Burnell to start instead of the experienced pair.
The other changes for the Grecians saw a place on the bench for new signing Troy Archibald-Henville as well as Craig McAllister, although it is believed Troy picked up an injury during the warm-up.
Burnell was making his first appearance at St James' Park for the first team and he was right at the heart of the action in the early stages when he did very well to rob 19-goal hitman Rickie Lambert as the striker lined up a shot at goal.
Corr made a goalscoring impact as a substitute on Saturday&nbsp;and he almost turned provider a minute later but Adam Stansfield couldn't quite get to the big striker's knockdown.
Andy Marriott spoke to the Official Website this week about the importance of stopping Lambert if the Grecians were to get anything from the game and Rob Edwards did exactly that on 14 minutes. Lallana's ball found the striker and after cutting inside Taylor the 37-year-old denied him just as it seemed he would pull the trigger.
Papa Waigo scored the third for the Saints when the teams met on Boxing Day and his first chance of the match came on 17 minutes, but well positioned the on-loan Fiorentina striker shot straight into Andy Marriott's midriff.
Returning youth product Dan Seaborne received a round of applause from the home fans before kick off and he had to swap his shirt for the first of three occasions soon after due to receiving a cut above his eye.
Richard Duffy, who was on top form last weekend, put in a vital sliding tackle before Morgan Schneiderlin shot at Marriott when well placed.
The match was struggling to spark into life with very little action at either end but any Grecians who were at St Mary's will have preferred this patient start to the disastrous opening 45 on Boxing Day.
Lloyd James scored the scoring that day and it was his cross that set up the opening goal that came in slightly controversial fashion, Matt Taylor believing he was fouled in the build up. James' ball was allowed to reach Lallana at the back post and he had time to compose himself before shooting into the far corner, past the despairing slide of Burnell.
Adam Stansfield and Liam Sercombe both had half-chances but couldn't find their range while new Saints signing, former Argyle man Jason Puncheon, drilled one effort into the Big Bank before acrobatically bicycling kicking on straight at City's number one.
Taylor then performed an inch-perfect slide tackle on Lambert before Waigo infuriated the City bench. The referee had blown for a foul and the ball fell to the Senegalise striker who smashed the ball towards the City bench from close range, provoking angry responses from some of the coaching staff.
Mr Haywood decided not to put Waigo's name in the book but he did chose to book Seaborne just two minutes after the break for a foul on Liam Sercombe and it was a foul that proved to be decisive.
From the resulting free-kick Stansfield won a corner and Golbourne stepped up to swing an accurate ball to the back post and there was Taylor to hammer a header past Davis.
The captain kissed his armband in front of his adoring public as he celebrated an almost carbon copy of his goal at St Mary's. City were level and the goal seemed to give them a shot in the arm.
Lambert wasted a good chance from Waigo's knockdown before the home side began to exert some real pressure and should have really taken the lead.
Harley found himself in space, as he has so often in this current formation, on the left-hand byline and running towards goal he decided to pick out the unmarked Corr inside the box. Corr couldn't quite get his feet right to take an effort and from the resulting scramble Harley couldn't find a way through.
Marriott justified his selection ahead of Paul Jones on Saturday and he proved just why Paul Tisdale recalled him with a very smart save from Lallana before Lambert fired wide after the resulting penalty area pinball.
Harley's top quality through ball to Adam Stansfield was then only spoilt by the linesman's flag while Golbourne's left-footed delivery minutes later was almost met by Corr.
At the other end Golbourne had City's hearts in their mouths when he almost headed a low cross past the onrushing Mariott.
With fifteen minutes to go Burnell's home debut came to an end and Cozic was introduced and the Frenchman did himself plenty of favours with some trademark runs and could have even doubled his League One tally!
Lambert has been a danger all season from free-kicks and many in the ground thought his heavily deflected 30yarder had found the top corner but the touch had been enough to send it just wide.
It was then City's set-piece king Harley's turn to try his luck, but his 86th minute effort flew just wide. Richard Logan was sent on for Adam Stansfield, who had battled on bravely despite picking up a knock, while the Saints introduced former Southend goal machine Lee Barnard.
Exeter City's games have rarely lacked late drama in recent weeks and it proved to be the same story again today.
We were one minute into the four added on when Cozic let rip with a lovely right-footed curling shot that seemed to only stay out and hit the woodwork thanks to the reflexes of the former Sunderland shotstopper.
But there was still time for some agonising Southampton pressure, &pound;1.2m transfer window signing Jose Fonte almost connecting with a corner but it just resulted in one final set-piece. City had conceded a last-gasp goal at home to Carlisle last time out but the misery would have been ten-fold had the familar face of Seaborne been celebrating.
But his shot, the second last kick of the game, landed on top of a relieved Marriott's goal.
Exeter: Marriott, Tully, Duffy, Taylor, Edwards, Golbourne, Harley, Burnell (Cozic 73),&nbsp; Sercombe, Stansfield (Logan 86), Corr.
Subs Not Used: Jones, McAllister, Dunne, Archibald-Henville, Fleetwood.
Southampton: Davis, Mills, Fonte, Seaborne, Otsemobor (Barnard 86), James (Thomas 79), Puncheon, Schneiderlin, Lallana, Lambert, Papa Waigo (Antonio 62). Keep visiting the Official Website this weekend for the views of Matt Taylor, Joe Burnell and Paul Tisdale as well as full highlights, photos and much more.
if (WIDGETBOX) WIDGETBOX.renderWidget('ad1286ad-9bc7-4b98-891e-66cc8cdf5eac');