The champions have slipped down to third in the table as a result of their dip in form, while Southampton are just three points clear of the relegation zone.
Southampton will be glad to see the back of 2018 - a year which has seen them pick up just six Premier League wins heading into their final game against Manchester City.
Such poor form saw them dragged into a relegation battle last season, and they are in the midst of another so far this term having won just three of their opening 19 games - only Huddersfield Town and Fulham have won fewer.
Two of those victories have come in four games under new boss Ralph Hasenhuttl, though, and there has been a definite improvement since the Austrian took charge earlier this month.
Defeats to Cardiff City and West Ham United suggest that there is still plenty more work to be done, but Hasenhuttl has already steered the Saints to successive league wins for the first time since April 2017, including a victory over Arsenal.
That win over the Gunners ended a 29-match winless streak against teams from the established top six, which will give them encouragement going into a double-header against Man City and Chelsea either side of the New Year.
Southampton have also scored seven league goals in their four games under Hasenhuttl, which is the same number as they managed in their 10 previous outings.
Having improved the attacking output, next on Hasenhuttl's list will be defensive work as his side go in search of a first clean sheet in 10 matches, although it would take some effort to earn that against the division's highest scorers this weekend.
The Saints have only won one of their 10 league games against teams in the top half of the table so far this term, and that solitary triumph - against Arsenal earlier this month - is also their only home win from nine outings at St Mary's this season.
Thursday's 2-1 reverse to West Ham was their first home loss since October 7, though, and a repeat result this weekend would condemn them to successive defeats in front of their own fans for the first time since September 2017.
The West Ham result also means that Southampton have now thrown away a league-high 15 points from winning positions this season, and Hasenhuttl will be acutely aware that his side cannot afford to keep surrendering leads so easily if they are to avoid another nail-biting relegation battle.
Recent Premier League form: DLLWWL
It has been a blue Christmas for the kings of English football, whose swagger and air of invincibility seems to have deserted them at a very inopportune moment.
Just three weeks ago Man City were being mentioned as one of the greatest teams this country has ever seen, and even Liverpool's relentless form was being overshadowed by Pep Guardiola's defending champions.
However, three defeats in their last four league games - as many as they had suffered in their previous 70 - have changed the whole landscape of the league to leave City third and now seven points adrift of leaders Liverpool.
Playing catch-up is not something these City players are used to doing; at the halfway stage of last season they were already 13 points clear at the top of the table having incredibly dropped just two points from their opening 19 games.
Now, though, it is Liverpool who are streaking clear at the top and next Thursday's showdown against the Reds at the Etihad Stadium - Man City's first game of 2019 - is suddenly a must-win one for the champions.
City remain the leading goalscorers in the Premier League this season, but it is the defensive stats which have made the most difference, with the champions having conceded more than twice as many goals as Liverpool and failing to keep a clean sheet in any of their last nine matches across all competitions.
Guardiola has never suffered three successive league defeats during his time in charge of Man City, but that is a fate that could befall his side should Southampton join Crystal Palace and Leicester City in stunning their visitors on Sunday.
City will still be favourites to return to winning ways against their relegation-threatened hosts, but having gone almost two years without losing to a team outside the established top six, the last two results will have given every team belief that the champions can be toppled.
Further encouragement will be drawn from City's recent away record, which has seen them win just one of their last five games inside normal time across all competitions, including the Boxing Day defeat at the King Power Stadium.
The Citizens have not lost back-to-back away games since October 2016, but whereas last season they dropped only seven points on the road throughout the entire campaign, they have already dropped 10 in the first half of this term.
City's recent dip does not change the fact that they are a formidable team and they are by no means out of the title race yet, but Guardiola will know that another slip-up on Sunday could leave them with a mountain to climb in 2019, having scaled such incredible heights in 2018.
Recent Premier League form: WWLWLL
Recent form (all competitions): LWWWLL
Fabian Delph's red card at the King Power means that he is suspended for this match and will be replaced by Oleksandr Zinchenko, and there could be further changes elsewhere as Guardiola attempts to keep his squad fresh before Liverpool.
Southampton, meanwhile, are able to welcome Pierre-Emile Hojbjerg back into the team after he missed the defeat to West Ham through suspension.
Southampton possible starting lineup:
McCarthy; Bednarek, Yoshuida, Vestergaard; Valery, Hojbjerg, Romeu, Targett; Redmond, Ings, Armstrong
Man City possible starting lineup:
Ederson; Walker, Otamendi, Laporte, Zinchenko; De Bruyne, Gundogan, D Silva; Mahrez, Aguero, Sterling
Head To Head
Man City have won each of their last four matches against Southampton and could win this fixture five times in a row for the first time ever.
The most recent of those matches came in November, when Man City ran riot with a 6-1 victory at the Etihad Stadium which saw them race into a three-goal lead inside 18 minutes.
Southampton's only win in their last 11 league games against City did come at home, though, as Sadio Mane scored a hat-trick in a 4-2 victory in May 2016.
We say: Southampton 1-3 Man City
City no longer look like the all-conquering champions they did just a few short weeks ago, while Southampton already look harder to beat under Hasenhuttl. We are still backing Man City to come out on top, but it is not as sure an outcome as it might have been earlier this month.