| 14 Aug 21 | r01  | SouthportSouthport | 2 - 2 | Gloucester CityGloucester Ci |
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| 21 Aug 21 | r02 | Spennymoor Town FCSpennymoor To | 3 - 2 | SouthportSouthport |
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| 28 Aug 21 | r03 | SouthportSouthport | 1 - 1 | Kidderminster HarriersKidderminster |
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| 30 Aug 21 | r04 | AFC FyldeAFC Fylde | 2 - 1 | SouthportSouthport |
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| 04 Sep 21 | r05 | SouthportSouthport | 3 - 3 | Gateshead FCGateshead FC |
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| 11 Sep 21 | r06 | Brackley TownBrackley Town | 1 - 0 | SouthportSouthport |
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| 09 Oct 21 | r08 | YorkYork | 3 - 1 | SouthportSouthport |
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| 26 Oct 21 | r11 | SouthportSouthport | 3 - 0 | Darlington F.C.Darlington F. |
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| 30 Oct 21 | r12 | SouthportSouthport | 3 - 2 | Chester CityChester City |
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| 02 Nov 21 | r07 | SouthportSouthport | 0 - 0 | ChorleyChorley |
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| 13 Nov 21 | r14 | SouthportSouthport | 4 - 1 | Boston United FCBoston United |
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| 20 Nov 21 | r15 | LeamingtonLeamington | 1 - 1 | SouthportSouthport |
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| 23 Nov 21 | r09 | SouthportSouthport | 2 - 0 | Alfreton TownAlfreton Town |
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| 04 Dec 21 | r16 | SouthportSouthport | 2 - 0 | HerefordHereford |
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| 07 Dec 21 | r13 | GuiseleyGuiseley | 0 - 2 | SouthportSouthport |
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| 11 Dec 21 | r17 | Blyth SpartansBlyth Spartan | 1 - 2 | SouthportSouthport |
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| 26 Dec 21 | r18 | CurzonCurzon | 0 - 0 | SouthportSouthport |
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| 28 Dec 21 | r19 | SouthportSouthport | 4 - 0 | Farsley CelticFarsley Celti |
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| 18 Jan 22 | r22 | SouthportSouthport | 1 - 0 | Bradford Park AvenueBradford Park |
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| 22 Jan 22 | r23 | Gloucester CityGloucester Ci | 0 - 1 | SouthportSouthport |
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| 29 Jan 22 | r24 | SouthportSouthport | 2 - 1 | GuiseleyGuiseley |
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| 01 Feb 22 | r10 | Kettering TownKettering Tow | 2 - 1 | SouthportSouthport |
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| 05 Feb 22 | r25 | Chester CityChester City | 5 - 0 | SouthportSouthport |
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| 08 Feb 22 | r21 | AFC Telford UnitedAFC Telford U | 0 - 3 | SouthportSouthport |
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| 12 Feb 22 | r26 | Boston United FCBoston United | 1 - 1 | SouthportSouthport |
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| 15 Feb 22 | r20 | SouthportSouthport | 0 - 0 | CurzonCurzon |
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| 22 Feb 22 | r28 | SouthportSouthport | 2 - 3 | Blyth SpartansBlyth Spartan |
| |
| 26 Feb 22 | r29 | HerefordHereford | 0 - 1 | SouthportSouthport |
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| 05 Mar 22 | r30 | SouthportSouthport | 0 - 0 | Brackley TownBrackley Town |
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| 12 Mar 22 | r31 | ChorleyChorley | 2 - 1 | SouthportSouthport |
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| 19 Mar 22 | r32 | SouthportSouthport | 3 - 3 | YorkYork |
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| 22 Mar 22 | r33 | Darlington F.C.Darlington F. | 1 - 0 | SouthportSouthport |
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| 26 Mar 22 | r34 | Alfreton TownAlfreton Town | 2 - 2 | SouthportSouthport |
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| 02 Apr 22 | r35 | SouthportSouthport | 0 - 1 | Kettering TownKettering Tow |
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| 09 Apr 22 | r36 | Kidderminster HarriersKidderminster | 6 - 0 | SouthportSouthport |
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| 12 Apr 22 | r27 | SouthportSouthport | 1 - 1 | LeamingtonLeamington |
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| 15 Apr 22 | r37 | SouthportSouthport | 0 - 0 | AFC FyldeAFC Fylde |
| |
| 18 Apr 22 | r38 | Farsley CelticFarsley Celti | 2 - 0 | SouthportSouthport |
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| 23 Apr 22 | r39 | SouthportSouthport | 1 - 1 | Spennymoor Town FCSpennymoor To |
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| 30 Apr 22 | r40 | Gateshead FCGateshead FC | 3 - 1 | SouthportSouthport |
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| 02 May 22 | r41 | SouthportSouthport | 1 - 1 | AFC Telford UnitedAFC Telford U |
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| 07 May 22 | r42 | Bradford Park AvenueBradford Park | 0 - 5 | SouthportSouthport |
Team 2021-2022 Schedules
AFC Telford United
Bedford Town
Brackley Town
Buxton
Chester
Chorley
Darlington
Harborough Town
Hebburn Town
Hednesford Town
Hereford
King's Lynn Town
Macclesfield
Marine
Merthyr Town
Morecambe
Oxford City
Radcliffe
Scarborough Athletic
South Shields
Southport
Spalding United
Spennymoor Town
Worksop Town
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