Southampton will face Everton at Goodison Park in their opening game of the 2021/22 Premier League season.
The Saints will then host Manchester United at St Mary's before they visit Newcastle to conclude their opening month of league fixtures in August.
Premier League champions Manchester City will make the journey to the south coast on September 18.
- In full: All the 2021/22 Premier League fixtures
- Find out more about Sky Sports
- 2012/22 Premier League kits
Ralph Hasenhuttl's side welcome newly-promoted Brentford on December 18 ahead of a trip to face West Ham at the London Stadium on Boxing Day, while Newcastle are the visitors on New Year's Day.
Southampton host London clubs Chelsea and Arsenal in successive league games in April, before they conclude their campaign at Leicester.
Southampton's 2021/22 Premier League fixtures
All fixtures subject to change.
August
14: Everton (a) - 3pm
22: Manchester United (h) - 2pm, live on Sky Sports
28: Newcastle United (a) - 3pm
September
11: West Ham United (h) - 3pm
18: Manchester City (a) - 3pm
25: Wolves (h) - 3pm
October
2: Chelsea (a) - 3pm
16: Leeds United (h) - 3pm
23: Burnley (h) - 3pm
30: Watford (a) - 3pm
November
6: Aston Villa (h) - 3pm
20: Norwich City (a) - 3pm
27: Liverpool (a) - 3pm
December
1: Leicester City (h) - 7:45pm
4: Brighton (h) - 3pm
11: Arsenal (a) - 3pm
14: Crystal Palace (a) - 8pm
18: Brentford (h) - 3pm
26: West Ham United (a) - 3pm
28: Tottenham Hotspur (h) - 3pm
January
1: Newcastle United (h) - 3pm
15: Wolves (a) - 3pm
22: Manchester City (h) - 3pm
February
9: Tottenham Hotspur (a) - 7:45pm
12: Manchester United (a) - 3pm
19: Everton (h) - 3pm
26: Norwich City (h) - 3pm
March
5: Aston Villa (a) - 3pm
12: Watford (h) - 3pm
19: Burnley (a) - 3pm
April
2: Leeds United (a) - 3pm
9: Chelsea (h) - 3pm
16: Arsenal (h) - 3pm
23: Brighton (a) - 3pm
30: Crystal Palace (h) - 3pm
May
7: Brentford (a) - 3pm
15: Liverpool (h) - 3pm
22: Leicester City (a) - 4pm
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Key dates for the 2021/22 season
The 2021/22 Premier League will start on Saturday August 14 - 34 days after the Euro 2020 final at Wembley.
The season will end on May 22 2022, with all 10 games kicking off at the same time.
The 2021/22 EFL season will kick-off on Saturday August 7.
Next season's League One campaign will finish on the weekend of April 30 2022, with League Two and the Championship on one of May 7 and May 8 respectively.
The League One play-off final will then be held on Saturday May 21, the League Two play-off final on Saturday May 28, and the Championship play-off final on Sunday May 29.