| 24 Jul 21 | r01        | Hansa RostockHansa Rostock | 1 - 3 | KarlsruheKarlsruhe |
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| 30 Jul 21 | r02        | KarlsruheKarlsruhe | 3 - 0 | DarmstadtDarmstadt |
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| 14 Aug 21 | r03        | SandhausenSandhausen | 0 - 0 | KarlsruheKarlsruhe |
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| 21 Aug 21 | r04        | KarlsruheKarlsruhe | 0 - 0 | Werder BremenWerder Bremen |
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| 27 Aug 21 | r05        | NurnbergNurnberg | 2 - 1 | KarlsruheKarlsruhe |
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| 11 Sep 21 | r06        | KarlsruheKarlsruhe | 2 - 2 | Holstein KielHolstein Kiel |
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| 17 Sep 21 | r07        | Schalke 04Schalke 04 | 1 - 2 | KarlsruheKarlsruhe |
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| 25 Sep 21 | r08        | KarlsruheKarlsruhe | 1 - 3 | St PauliSt Pauli |
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| 02 Oct 21 | r09        | Jahn RegensburgJahn Regensbu | 2 - 2 | KarlsruheKarlsruhe |
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| 16 Oct 21 | r10        | KarlsruheKarlsruhe | 2 - 1 | AueAue |
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| 23 Oct 21 | r11        | Fortuna DüsseldorfFortuna Düsse | 3 - 1 | KarlsruheKarlsruhe |
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| 31 Oct 21 | r12        | KarlsruheKarlsruhe | 2 - 4 | PaderbornPaderborn |
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| 06 Nov 21 | r13        | KarlsruheKarlsruhe | 1 - 1 | HamburgHamburg |
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| 21 Nov 21 | r14        | IngolstadtIngolstadt | 1 - 1 | KarlsruheKarlsruhe |
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| 27 Nov 21 | r15        | KarlsruheKarlsruhe | 4 - 0 | HannoverHannover |
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| 05 Dec 21 | r16        | Dynamo DresdenDynamo Dresde | 3 - 1 | KarlsruheKarlsruhe |
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| 12 Dec 21 | r17        | KarlsruheKarlsruhe | 3 - 2 | FC HeidenheimFC Heidenheim |
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| 19 Dec 21 | r18        | KarlsruheKarlsruhe | 2 - 2 | Hansa RostockHansa Rostock |
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| 15 Jan 22 | r19        | DarmstadtDarmstadt | 2 - 2 | KarlsruheKarlsruhe |
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| 05 Feb 22 | r21        | Werder BremenWerder Bremen | 2 - 1 | KarlsruheKarlsruhe |
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| 08 Feb 22 | r20        | KarlsruheKarlsruhe | 0 - 2 | SandhausenSandhausen |
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| 12 Feb 22 | r22        | KarlsruheKarlsruhe | 4 - 1 | NurnbergNurnberg |
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| 19 Feb 22 | r23        | Holstein KielHolstein Kiel | 0 - 2 | KarlsruheKarlsruhe |
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| 26 Feb 22 | r24        | KarlsruheKarlsruhe | 1 - 1 | Schalke 04Schalke 04 |
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| 05 Mar 22 | r25        | St PauliSt Pauli | 3 - 1 | KarlsruheKarlsruhe |
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| 13 Mar 22 | r26        | KarlsruheKarlsruhe | 1 - 1 | Jahn RegensburgJahn Regensbu |
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| 18 Mar 22 | r27        | AueAue | 0 - 3 | KarlsruheKarlsruhe |
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| 03 Apr 22 | r28        | KarlsruheKarlsruhe | 2 - 2 | Fortuna DüsseldorfFortuna Düsse |
| |
| 10 Apr 22 | r29        | PaderbornPaderborn | 2 - 2 | KarlsruheKarlsruhe |
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| 16 Apr 22 | r30        | HamburgHamburg | 3 - 0 | KarlsruheKarlsruhe |
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| 22 Apr 22 | r31        | KarlsruheKarlsruhe | 2 - 2 | IngolstadtIngolstadt |
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| 29 Apr 22 | r32        | HannoverHannover | 2 - 0 | KarlsruheKarlsruhe |
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| 08 May 22 | r33        | KarlsruheKarlsruhe | 2 - 2 | Dynamo DresdenDynamo Dresde |
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| 15 May 22 | r34        | FC HeidenheimFC Heidenheim | 2 - 0 | KarlsruheKarlsruhe |