Ivan Juric's side sit at the foot of the table with a measly nine points from 28 games and suffered their 23rd defeat of the season at Liverpool on Saturday.
Saints have averaged a win every 14 league games but a single victory between now and May 25 would see them surpass Derby County's unwanted record.
The Rams claimed 11 points during the 2007-08 Premier League season. We have taken a look at where Saints can win points to avoid writing their names in the history books.
Southampton could be relegated within the next three games.Southampton could be relegated within the next three games. (Image: Stuart Martin) Wolves (H) - Saturday, March 17
Southampton's best chance of claiming another three points at home this season comes against Wolves this weekend.
Vitor Pereira's side sit 17th in the Premier League table but have a massive 14-point gap between themselves at lowly Southampton.
The margin to safety will grow to 17 points if Juric's charges suffer their 12th defeat at St Mary's this season.Southampton suffered a controversial 2-0 defeat at Wolves earlier this season.Southampton suffered a controversial 2-0 defeat at Wolves earlier this season. (Image: Jacob King/PA) Crystal Palace (H) - Wednesday, April 2
Saints return to action after the international break with a game against Crystal Palace under the lights at St Mary's.
Oliver Glasner's side will have faced Fulham in the FA Cup three days previously, potentially giving Saints an upper hand.
Crystal Palace beat Southampton 2-1 at Selhurst Park earlier this season.Crystal Palace beat Southampton 2-1 at Selhurst Park earlier this season. (Image: PA) Tottenham Hotspur (A) - Sunday, April 6
Southampton could be relegated at Tottenham if they lose their next three games and other results go against them.
Wolves will need to beat Saints, West Ham and Ipswich Town to condemn the south coast side to Championship football.
Saints would become the first team to be relegated in game week 31, beating the current earliest relegation record held by Huddersfield and Derby (game week 32).
Tottenham Hotspur thumped Saints 5-0 at St Mary's this season, leading to Russell Martin's sacking.Tottenham Hotspur thumped Saints 5-0 at St Mary's this season, leading to Russell Martin's sacking. (Image: PA) Aston Villa (H) - Saturday, April 12
Saints could realistically be relegated if they suffer defeat in any of the following games.
Juric's side will be down should Wolves win at St Mary's and claim two more points from the three fixtures which follow.
Villa are still fighting on three fronts - Premier League, Champions League and FA Cup - so Unai Emery may take mercy on Saints and rotate his side.
Aston Villa won 1-0 against Saints at Villa Park in December.Aston Villa won 1-0 against Saints at Villa Park in December. (Image: PA) West Ham (A) - Saturday, April 19
Lose the next five games and Saints will be relegated, regardless of other results. The gap to Wolves will be at least 17 points with only 15 points left to win.
Saints won their first Premier League game at the London Stadium 3-0 in September 2016 to move to 9th in the table.
Alex McCarthy was on the bench that day but could suffer his second relegation in red and white nearly a decade later. Cue the James Ward-Prowse winner.
West Ham were 1-0 winners against Saints in Ivan Juric's first game in charge.West Ham were 1-0 winners against Saints in Ivan Juric's first game in charge. (Image: PA) Fulham (H) - Saturday, April 26
If Saints have not won a game by this stage, setting a new record-low points total will become a serious concern.
At the time of writing, Fulham have won more games on the road (six) than they have done at Craven Cottage this season (five).
Ivan Juric was in the stands when Saints drew 0-0 with Fulham in December.Ivan Juric was in the stands when Saints drew 0-0 with Fulham in December. (Image: Southampton FC/PA) Leicester City (H) - Saturday, May 3
Of all the remaining games, this is Southampton's best chance on paper of winning another game and saving themselves from eternal embarrassment.
Fellow promoted side Leicester City are struggling at the foot of the table but are only six points from safety at the time of writing.
Saints had an almighty collapse against Leicester at St Mary's earlier this season, throwing away their 2-0 lead to lose 3-2.
Leicester City have won their last three games against Southampton.Leicester City have won their last three games against Southampton. (Image: John Walton/PA) Manchester City (H) - Saturday, May 10
Need we say much here? Manchester City are performing at a level far below their usual standard but Pep Guardiola's side will be battling out for a Champions League spot.
They will welcome a trip to the south coast where Saints have conceded 37 goals in 13 games at the time of writing.
Manchester City claimed a narrow 1-0 win over Saints earlier this season.Manchester City claimed a narrow 1-0 win over Saints earlier this season. (Image: PA) Everton (A) - Sunday, May 18
Saints are guaranteed to make a bit of history before the end of the season as they will be Everton's final opponents at Goodison Park.
The Toffees have already lost twice against Southampton this season but have picked up since David Moyes returned to the club.
Saints won on penalties at Goodison Park earlier this season.Saints won on penalties at Goodison Park earlier this season. (Image: PA) Arsenal (H) - Sunday, May 25
This long, horrible season comes to an end at St Mary's when Saints welcome Arsenal to the south coast.
Mikel Arteta's side are currently second but stand next to no chance of catching league leaders Liverpool so both teams could have nothing to play for other than pride.
Saints lost 3-1 at Arsenal earlier this season.Saints lost 3-1 at Arsenal earlier this season. (Image: PA)