The Black Cats advanced from the last stage with a 2-0 home win over Peterborough United of League One, while Saints emerged from the third round with a comfortable 2-0 victory over third-tier outfit Bristol City at St Mary's.
However, Sunderland booked their place in the last eight with a narrow win on the night.
Read how the match unfolded in our live commentary.
6.49pmGood evening and welcome to Sports Mole's live coverage from the Capital One Cup where Sunderland host Southampton at the Stadium of Light.
6.52pmWhile many will be concentrating on the likes of Arsenal, Chelsea and Celtic in the Champions League, our focus is on the Capital One Cup, and we have a cracking all-Premier League tie for you.
6.56pmIt's a clash of the teams in red and white stripes as Sunderland and Southampton duel for a place in the fifth round of the competition.
6.57pmSunderland made it to this phase of the tournament after beating League One side Peterborough United 2-0 at the Stadium of Light in the third round. Emanuele Giaccherini and Valentin Roberge were on the scoresheet that night.
7pmOn the other hands, Saints progressed from the third stage by getting the better of Bristol City, also of League One, at St Mary's thanks to goals from Gaston Ramirez and Jos Hooiveld.
7.33pm20-year-old midfielder Lloyd Isgrove, 19-year-old Jack Stephens and 18-year-old Sam Gallagher all get a place among the substitutes.
7.35pmPochettino has also named two 18-year-old's in the starting XI, right-back Callum Chambers and midfielder Harrison Reed.
7.36pmWe're just under 10 minutes away from kick off at the Stadium of Light.
7.42pmThe teams are in the tunnel at the Stadium of Light.
7.44pmAnd out they come to cheers out onto the field.
7.45pmKelvin Davis captains Southampton tonight, as he returns to face his former club.
7.46pmSunderland are wearing their red and white striped home kit with black shorts and red socks. Saints are in their all black/grey away strip.
1 minKICK OFF! Saints get us underway at the Stadium of Light.
4 minNearly a chance for Saints as Chambers whips in a low cross from the right, but Tadanari is just beaten to the ball by O'Shea.
6 minTadanari gets in a shot after Ramirez dribbles himself out of a tight situation, but the effort is high and over the crossbar.
8 minJust a reminder that the winner of this will be rewarded with a home tie in the quarter-finals against Chelsea.
9 minSaints have a corner which is curled in from the right, it drops of a head and Rodriguez is in quickly to try to get a shot away, but it's blocked and out for a goal kick.
9 minCHANCE! First attacking bit of play from Sunderland of the night as Bardsley plays a long ball down the right to Altidore. He uses his strength to hold off Fox and he comes inside and get into the box, but his low shot crawls along the floor and comfortably into the arms of Davis.
12 minIt's been an even start to the match, but Saints have perhaps slightly edged it so far in terms of possession. Best chance has fallen to Sunderland though, albeit the only clear chance.
15 minCHANCE! Promising move from Sunderland down the right as Celustka pulls a low cross back to Giaccherini, but he hits the ball off his standing foot and out for a goal kick, albeit with a fair bit of power.
17 minMust be said that there are a lot of empty seats at the Stadium of Light tonight and it's fairly quiet as a consequence.
19 minSunderland are having a good spell of possession in Southampton's half at the moment, but they can't seem to find that decisive pass. Saints are pressing a lot.
22 minBardsley cuts onto his right foot on the left of the field and chips a cross towards the far post, but it is just too high for Craig Gardner, and it goes out for a goal kick.
26 minSunderland are enjoying a bit more attacking play at the moment, but we still haven't had a clear chance for a while.
27 minCHANCE! Altidore has a go at goal after bring the ball down 25 yards out. It was always ambitious from the USA international, and it flew wide along the ground past the near post. Davis was never going to be troubled by that.
31 minCHANCE! The ball bobbles about in the penalty area from a Sunderland corner, and it falls to Colback on the left of the box. He hits it with his left but drags it wide of the far post.
32 minKudos to the Southampton fans who have travelled up to this match. It's heck of a long trip to make for a wet and windy Wednesday night.
36 minSaints are just starting to come back into it now and get a bit more of the ball, but they haven't tested Mannone at all yet.
40 minSunderland have floated a few balls into the box, but they've been too close to Davis each time, and he's collected them easily.
44 minCHANCE! The best chance of the half falls to Saints, and Gaston Ramirez. On the edge of a busy box, Cork slots a brilliant pass out to him on the right of the box and Ramirez hits it high and wide first time.
59 minIt's a scrappy one but they all count, and it's Bardsley's first goal for Sunderland. The free kick is curled into the box from the left. Brown gets his head to it and it's saved by Davis, but nobody clears it away and Bardsley can't help the loose ball over the line.
63 minSaints have responded well with few corners and lofted free kicks into the box, but they haven't managed to stump up a chance on goal yet.
65 minSaints want a penalty after Chambers goes down in the box, but the referee gives nothing.
68 minCelustka is hobbling off the field and down the tunnel. That will be the end of his night but he hasn't been replaced yet. Larsson will come on shortly, but Sunderland are down to 10 men for now.
70 minSUNDERLAND CHANGE Sebastian Larsson comes on to replace the injured Celustka.
70 minSAINTS CHANGE Pochettino are also going to make a change, and Lallana is called on for Steve Davis.
71 minCLOSE! Ward-Prowse swings a corner into the far post, but Yoshida heads it over.
74 minNearly an embarrassing moment for Sunderland, as O'Shea gives an awkward pass back to Mannone, who doesn't have much time and boots it clear. However, it cannons off the back of an onrushing Lallana, but it flies just wide of the open goal.
75 minYELLOW CARD Hooiveld is booked for kicking the ball away. Silly thing to do.
77 minGardner has a chance from free kick about 30 yards from goal, but his wild effort is horrendously hit over the bar.
79 minSAINTS CHANGE Gaston Ramirez is taken off, with Sam Gallagher coming on.
80 minGallagher, a product of the Saints academy, is making his debut for the side here.
81 minKi is currently down receiving treatment and looks in pain. Poyet may be forced into making a second change here.
83 minKi hobbles off to the side of the pitch, but he is going to continue here.
84 minHalf-hearted appeals from Saints for a penalty as Lallana goes down up against Gardner, but Lee Mason doesn't give one.
86 minLarsson surely puts Sunderland into the last eight with a decisive second goal. Giaccherini is brilliantly tackled by the last man Danny Fox, but that leaves the left-back out of position. Altidore picks up the loose ball and rolls it to Larsson on his right in space, who drills a shot into the bottom corner. Game over.
88 minI knew Saints would score as soon as I typed 'game over'. It may be a little too late, but a brilliant Ward-Prowse free kick to the far post was nodded back across goal by Hooiveld before Yoshida headed in to get Saints back in it.
89 minGiaccherini wants to come off injured and is unable to move freely on the side of the field. Sunderland down to 10 for the last few minutes.
90 minGiaccherini looks as if he has just pulled a muscle in his back, he is going to be replaced by Fletcher.