Head coach Tonda Eckert has said Saints - unbeaten in the last 14 games - will not view this game against the Premier League leaders as a free hit.
They could provide a memorable cup upset by beating the Champions League outfit at St Mary's, denying them the chance to win a famous treble.
The St Mary's side extinguished Manchester City's quadruple hopes under Nathan Jones in 2022/23 by beating them 2-0 in the Carabao Cup.
And beyond the chance of reaching Wembley, Bree also knows that beating Arsenal would boost spirits as Saints aim for a Premier League return.
"We're all really excited. It's a really good opportunity for us and a good challenge against an unbelievable team," he told the Daily Echo.
James Bree scored an FA Cup winner against Leicester in the fourth round.James Bree scored an FA Cup winner against Leicester in the fourth round. (Image: Stuart Martin)
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"We know it's going to be a tough game, but it's something we're really excited for. We're in a really good run of form at the moment.
"Momentum is really key. We're on a really good run, and that's something that you don't want to break when you're doing so well.
"We want to go and progress to the next round and keep that run going. It's an important one for us. We'll be going into it and trying our best."
A 14-game unbeaten run has seen Saints beat Championship leaders Coventry and Premier League Fulham, but can these occasions bring nerves?
"Sometimes it does. It just depends on when you turn up at the ground, if you get that different feel. I think it goes game by game," Bree admitted.
"Sometimes you might have that extra bit of nerves, sometimes you feel really calm. I think it just depends on the day, really."