Saints and the Whites will each be without key players for this weekend's sell-out in North London, across several different areas of the pitch.
While some players are in with a chance of making the bench at Wembley, others are ruled out indefinitely and will be forced to watch their teammates from the stands, alongside the 90,000-or-so spectators packed into the national stadium.
Here is a breakdown of the injuries and doubts on either side of the red and white divide ahead of this weekend's clash.
1. Gavin Bazunu - (ankle)
The Irish international goalkeeper ruptured his Achilles late in the season and is sidelined for several months. Photo: George Wood/Getty Images
2. Juan Larios - (out)
Former Manchester City youth team left-back Larios has not featured for the Saints since November 2022 due to a series of injuries and fitness issues. Photo: Warren Little
3. Stuart Armstrong - (doubt)
Scottish international Armstrong will have one eye on this summer's European Championships with Scotland under national team boss Steve Clarke, whose provisional squad he has been named in this week. The 32-year-old has been ruled out lately with a quadriceps injury but could make a return at Wembley to prove his fitness to Clarke, if he is able to convince club manager Russell Martin. Photo: Andrew Milligan
4. Stuart Dallas - (out)
The veteran midfielder has already announced his retirement for the end of the season, unable to come back from a horror leg break sustained two years ago, close enough to the level at which he previously played and would be required for such a big game. | Getty Images
5. Sam Byram (doubt)
Byram missed last week's 4-0 demolition of Norwich City in the play-off semi-final second leg with a hip flexor problem and is unlikely to come back into the starting XI at Wembley as a result, even if he is passed fit to make the squad. Photo: Ian Hodgson
6. Pascal Struijk - (groin)
Central defender Struijk has had to sit on the sidelines watching Ethan Ampadu and Joe Rodon strike up a strong defensive partnership during the second half of the season. The Dutchman's last appearance came on Boxing Day away at Preston North End and has since undergone surgery on a groin issue. | Getty Images