Southampton have suffered their first defeat in the Europa League as Inter Milan sealed a 1-0 victory against the run of play at San Siro on Thursday night.
Claude Puel's men dominated the first half, but they were left to rue their missed opportunities as a 67th-minute goal from Antonio Candreva ended up being the difference.
Before tonight, Frank de Boer's side had not picked up a point in Group K following back-to-back defeats, but they now have their first positive result in the bag.
The Saints almost caused a problem for themselves in the fourth minute when Mauro Icardi latched on to Cuco Martina's poor back pass, but the forward's back-heel failed to find a teammate.
Icardi's feud with his own supporters is ongoing, and he struggled to make an impact in the fist half as Southampton dominated the ball.
Jay Rodriguez wasted a handful of opportunities, one of which resulted in him running straight into Miranda in the box after finding acres of space with the ball.
The forward was also inches away from getting a touch on the ball when it was crossed into the area by Sam McQueen, but Yuto Nagatomo ended up clearing off the line.
Towards the end of the half, Rodriguez was involved again when Martina whipped the ball into the box to find Shane Long, who headed across the face of goal, but his teammate failed to get the tap-in.
James Ward-Prowse delivered some pin-point crosses into the danger area, but they came to nothing in the first half. On one occasion, Virgil van Dijk failed to attack the ball as he watched it bounce behind for a goal kick.
The 21-year-old also came close to scoring when his first-time shot from the edge of the penalty area grazed the top of the crossbar.
Inter's goalscoring opportunities were few and far between in the first half as they struggled to find a way through their opponents and appeared to lack desire.
However, as the half-time break edged closer, the hosts improved on the ball and Eder almost caused trouble when he broke into the box, but he slowed down before unleashing a shot, which gave Maya Yoshida time to get across and block.
The forward had another chance a few minutes later when a ball played over the top was headed down towards Eder's feet. The Brazilian took a touch before delivering a low strike just past the post.
After the break, Inter looked more lively as they tried to close down their opponents while off the ball, but Southampton also looked to cause trouble.
Rodriguez was played through on goal, but Miranda did well to get across and stop the forward in his tracks with a well-timed tackle.
The resulting corner ended up with the ball in the back of the net after Rodriguez headed in from the centre of the box, but the referee disallowed the goal due to the striker climbing on the back of Davide Santon.
At the other end of the pitch, Eder played in Icardi in the box, but the forward's strike, which was aiming for the top corner, fizzed inches wide of the target.
Charlie Austin, who replaced the injured Long, squandered an opportunity shortly after coming off the substitutes' bench as he picked up the ball on the edge of the box but drilled his shot wide.
Southampton suffered a huge blow when Inter took the lead against the run of play in the 67th minute as Candreva latched on to a low cross into the box before smashing the ball into the top corner.
Inter had their tails up after nudging in front, and with it came a wave of confidence among the players as Icardi showed decent skill in the box by turning away from two defenders before unleashing a shot, but his attempt was blocked.
Southampton were given somewhat of a lifeline when Marcelo Brozovic was sent off for a second bookable offence with 12 minutes left on the clock, but they failed to make the most of it.
Van Dijk came close to finding an equaliser when he got on the end of Ward-Prowse's cross, but his close-range shot went directly to the keeper.
In the final two minutes of normal time, Inter desperately held on as Van Dijk's header was cleared off the line and Austin's close-range strike was saved by Samir Handanovic.
The result keeps Southampton second in Group K, two points behind leaders Sparta Prague, while Hapoel Be'er Sheva sit third and Inter remain bottom, one point off the top two.