Jota returned after 11 games out to score the late equaliser in the 2-2 draw with Fulham on Saturday - his fifth goal of the season in 11 appearances.
The Portuguese attacker was in contention to start at St Mary's, with Slot likely to rotate where he can ahead of busy few weeks for the Reds.
In order to build up his match fitness, a start against the Saints would have been likely, but those plans have been scuppered by another setback, with Jota not taking part in training on Monday.
Jota to miss EFL Cup quarter-final?
Speaking in his pre-match press conference ahead of the trip down south, Slot confirmed that Jota is a doubt for the quarter-final tie.
"Diogo would have been definitely one that was ideal for him to play, but after the game, he wasn't completely fit." Slot announced.
"He didn't train with us yesterday so let's see if he can train with us today."
Slot admitted it is unlikely he will be fit enough to play from the start, with Jota still feeling discomfort from the abdominal issue that ruled him out for almost two months.
"Don't expect him to start. Hopefully he can make some minutes but I don't expect him to start tomorrow"
Jota's never-ending injury troubles
This recent abdominal issue may be new for Jota, but injury concerns in general are certainly not for a player that has been held back by fitness problems for many years.
When on the pitch, Jota's quality is there for all to see, and his goalscoring record backs that up.
Since moving to English football in 2017, Jota has hit double figures for goals in all but one of those seven seasons, with the only outlier being the 2022-23, when he missed the majority through injury.
Jota missed 29 games that year, another 25 last season, and he has already been absent for 13 this time around, in what continues to be a frustrating occurrence for the 28-year-old.
Written by
Andrew Delaney