If it isn't a must win match for both teams, it's certainly a must not lose.
Everton are flirting dangerously close to the relegation zone, which The Saints are in - while the home side's last experience at St Mary's was that chastening 9-0 demolition by Leicester.
We asked out Everton writer Adam Jones for his verdict on the South Coast showdown.
Win, lose or draw?
Surely Everton have got to end this horrid run of away form soon?
The Blues' record is actually even worse on the south coast, having not won in the area since a 3-0 win over Southampton back in August 2015.
Trips to the Saints, Bournemouth and Brighton since have been a tough slog, but Marco Silva will be keen to put that right.
Everton performed well generally in their last away game and are coming into this match on the back of a win and a draw at Goodison Park.
The Blues should be looking to win this - and are just about favourites with thepools.com to do just that. They are 7/5 to triumph .
Who's a good bet for first scorer?
Gylfi Sigurdsson has scored on each of his last two visits to St Mary's - and unfortunately he was Everton's only scorer on both occasions.
The Icelandic international hasn't started a game since the 1-0 defeat to Burnley last month, but injury issues may force Silva's hand this time around.
If the 30-year-old starts, he wouldn't be a bad bet to score first. He's a 15/2 tip to score first and 11/4 to score at any time .
Who's on pens?
If Sigurdsson is indeed named in the starting line-up, you'd expect he will be on penalty duty if the time comes.
Although, his record with them isn't exactly the best, and some supporters have called for someone else to step up.Lucas Digne could be that man, but you'd still expect the main taker to be Sigurdsson. See above ....
Will Everton keep a clean sheet?
Clean sheets have been very few and far between for Everton this season.
And only one of the three they have managed in the league so far has come away from home - a drab 0-0 draw with Crystal Palace on the opening day of the term. Both Teams To Score is 7/10 while Both Teams Scoring and Either Side To Win is 6/4 .
So, going on that, you'd have to say no.
Yellow card
Injury issues could well hand another opportunity to Morgan Schneiderlin, and we all know he's not exactly one to shy away from a booking.
Coming up against his former club too, all the cards might have fallen into place here.
