City travel down to the south coast hoping to secure a 13th-successive Premier League victory in Saturday's 17:30 (UK) kick-off.
However, Southampton are unbeaten in seven matches on home soil, with their only defeat at St. Mary's Stadium this season coming back in September.
Ralph Hassenhuttl's side won't make life easy for City, and will harbour fond memories from our last encounter, when they came away from the Etihad Stadium with a point in September's reverse fixture.
It leaves FPL managers with plenty to ponder ahead of Friday's 18:30 (UK) deadline.
Thankfully, as part of our weekly series, the Scout is on hand to provide one City player, one opponent and another Premier League star they expect to stand out this weekend.
Check out the latest FPL Scout Report below...
Kevin De Bruyne (£12.1m) visits Southampton in Gameweek 23 in his best form of 2021/22 Fantasy Premier League.
The City playmaker scored the decisive goal in a 1-0 win over Chelsea last weekend, claiming 11 points.
That strike took his tally to four goals, an assist and 47 points over his last six matches.
The underlying numbers further highlight De Bruyne’s huge all-round influence on the Manchester City attack.
His totals of 22 shots and 20 chances created in his previous six outings are both among the top three players in Fantasy.
An ownership of just 11 per cent makes De Bruyne a major differential for Saturday evening’s encounter at St Mary’s Stadium.
Opponent to watch
Saints, meanwhile, have an in-form midfielder of their own. James Ward-Prowse (£6.3m) has four goals, two assists and 45 points in his last five matches.
Purple patch: James Ward-Prowse is currently the Premier League's fifth most in-form player, according to FPL statistics.
A player's result is calculated from their average score per match across the last 30 days, with the midfielder currently boasting a rating of 8.8.
Other Premier League pick
Trent Alexander-Arnold (£8.4m) and Emmanuel Dennis (£6.1m) are among the top captaincy picks for Gameweek 23.
Liverpool’s Alexander-Arnold faces Crystal Palace having produced seven double-figure hauls this season, joint-top in Fantasy.
Dennis hosts a Norwich City side who have conceded a league-high 45 goals in 2021/22.