United welcome the Saints to St. James' Park this weekend (3pm kick-off) just three days on from their penalty shoot-out defeat to Burnley, which saw their interest in the competition end at the second round stage.
But with the Magpies still seeking a first Premier League win of the campaign, and with the first international break of 2021/22 set to follow Saturday's clash, head coach Bruce wants his charges to do everything they can to put that game behind them and get themselves off the mark against Ralph Hasenhüttl's men.
"(We need to do) whatever it takes to win a match. Certainly, we defended much, much better against Burnley – that has to be a given if we're going to get anything out of the Premier League," he said.
"I don't think Burnley had a shot at our goal the other night – the goalkeeper didn't make a save. That was really, really pleasing and something that we have to address to make sure we've got a chance in the Premier League. We can't keep conceding the way we have done, so it was good to keep a clean sheet the other night.
"It's probably the worst way to go out, on penalties. There's a huge disappointment amongst (the players), as you would expect. For me they didn't deserve it, they should have went through in 90 minutes, but it didn't happen and we lost the lottery of a penalty shoot-out.
"We have to accept it, but the great thing about football is there is another game tomorrow. Let's hope we can erase it by trying to get a result tomorrow."
Bruce has a largely fit squad to select from this weekend, with only goalkeepers Martin Dúbravka and Karl Darlow definitely unavailable.
Allan Saint-Maximin is expected to shake off a knock and, while Paul Dummett is nearing a return, midfielder Isaac Hayden remains "touch and go" for the visit of the Saints.
"(Saint-Maximin) had a kick on the top of his foot, and it looks a little bit sore, but we expect him to be OK," said Bruce.
"We're all OK. We've got the same problem with the goalkeepers, but we’ve got Dummett in and around it.
"It's touch and go for Isaac Hayden, but everybody else seems to be OK. He trained a bit yesterday, but considering he was out for a good period of time last year with a knee injury, we'll have another look at him today and see what we think."
The last meeting between the two sides was an entertaining affair, with then-loanee Joe Willock's first goal for the club helping ten-man United to a 3-2 win back in February.
And Bruce anticipates another stern test at the hands of Hasenhüttl's side, who are likely to line up with former Magpies frontman Adam Armstrong in attack.
"Southampton play in a certain way and it'll be a decent game against them, that’s for sure," he said. "I expect a tough game, like they all are, and it's important that we get a result.
"We've got an international break coming up and we'd love to get some points on the board. We've only played two league games, so it's still very, very early.
"We've had some positive things to come out of those two league games, (but) haven't got the result which at the end of the day is what everybody needs. It would be nice to get a result before the break."
