Southampton open their campaign away to Crystal Palace on Saturday before welcoming Tottenham Hotspur to St Mary's in their first home game of the season.
The New Year could not get off to a much more difficult start as the Saints host Liverpool in their first match of 2021, and that kicks off a tricky January with Leicester and Arsenal also to come after that.
May begins with a home game against Leicester - the fixture they lost 9-0 in last season - and a trip to Anfield before ending the campaign away to West Ham United.
SEPTEMBER
12: Crystal Palace (a)
19: Tottenham (h)
26: Burnley (a)
OCTOBER
3: West Brom (h)
17: Chelsea (a)
24: Everton (h)
31: Aston Villa (a)
NOVEMBER
7: Newcastle (h)
21: Wolves (a)
28: Manchester United (h)
DECEMBER
5: Brighton (a)
12: Sheffield United (h)
15: Arsenal (a)
19: Manchester City (h)
26: Fulham (a)
28: West Ham (h)
JANUARY
2: Liverpool (h)
12: Leeds (a)
16: Leicester (a)
27: Arsenal (h)
30: Aston Villa (h)
FEBRUARY
2: Manchester United (a)
6: Newcastle (a)
13: Wolves (h)
20: Chelsea (h)
27: Everton (a)
MARCH
6: Sheffield United (a)
13: Brighton (h)
20: Tottenham (a)
APRIL
3: Burnley (h)
10: West Brom (a)
17: Crystal Palace (h)
24: Manchester City (a)
MAY
1: Leicester (h)
8: Liverpool (a)
12: Fulham (h)
15: Leeds (h)
23: West Ham (a)