Coach Graeme Murty ended playing career with the Saints
The 41-year-old ended his playing career with the Saints in 2010, before moving into coaching within the south coast outfit's youth setup.
Speaking to canaries.co.uk ahead of the game, Murty explained: "It's a game which is very close to my heart, first and foremost.
"I'm very thankful for them giving me an opportunity to play at such a big club, then for giving me such a good grounding as a coach. It's always nice to go to Staplewood, and I worked with the group we're up against.
"They're a good bunch but I'm determined for our team to do what we're good at. It's important I take myself to the side and let the players focus on their game, because that's the main thing."
City have already met Southampton twice this season, impressively securing a 3-2 away win at the end of January having drawn 2-2 at Colney three months earlier.
On what he learned from those contests, Murty added: "It's going to be a competitive game but will hopefully be one played in the right way.
"The players need to lay down a marker for next season. People are forming opinions of them every day, so they need to leave a positive impression with everyone in these closing weeks of the season.
"More importantly, they need to start to reach a level of consistency they are capable of. We've got a good group of first year scholars coming in, meaning the older players will have to work for their starting position next year."
L – 2-3 v Stoke City (H) 19/03/2016 - Barclays U18s Premier League
L – 0-1 v Swansea City (H) 12/03/2016 - Barclays U18s Premier League
D – 1-1 v Newcastle (A) 05/03/2016 - Barclays Under-18s Premier League
L – 2-0 v Manchester City (A) 29/02/2016 - FA Youth Cup
L – 2-5 v Brighton & Hove Albion (H) 27/02/2016 - Barclays Under-18s Premier League