| Offensive Starters | | | | | |
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| QB | Jimmy Garoppolo | 31 | 8 | 10 | 207 for 308, 2,437 yards, 16 td, 4 int, & 23 rushes for 33 yards and 2 td | |
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| RB | Christian McCaffrey* | 26 | 5 | 10 | 159 rushes for 746 yards, 6 td, & 52 catches for 464 yards and 4 td | |
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| FB | Kyle Juszczyk* | 31 | 9 | 12 | 7 rushes for 26 yards, 1 td, & 19 catches for 200 yards and 1 td | |
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| WR | Brandon Aiyuk | 24 | 2 | 17 | 78 catches for 1,015 yards, 8 td, & 2 rushes for 23 yards and 0 td | |
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| WR | Deebo Samuel | 26 | 3 | 12 | 56 catches for 632 yards, 2 td, & 42 rushes for 232 yards and 3 td | |
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| TE | George Kittle* | 29 | 5 | 15 | 60 catches for 765 yards, 11 td | |
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| LT | Trent Williams*+ | 34 | 12 | 14 | | |
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| LG | Aaron Banks | 25 | 1 | 16 | | |
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| C | Jake Brendel | 30 | 6 | 17 | | |
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| RG | Spencer Burford | 23 | Rook | 16 | | |
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| RT | Mike McGlinchey | 27 | 4 | 17 | | |
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| Defensive Starters | | | | | |
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| LDE | Samson Ebukam | 27 | 5 | 15 | 5.0 sacks, 0 interceptions, 1 fumble recovered | |
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| LDT | Kevin Givens | 25 | 3 | 11 | 2.0 sacks, 0 interceptions, 0 fumbles recovered | |
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| RDT | Arik Armstead | 29 | 7 | 9 | | |
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| RDE | Nick Bosa*+ | 25 | 3 | 16 | 18.5 sacks, 0 interceptions, 0 fumbles recovered | |
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| LLB | Azeez Al-Shaair | 25 | 3 | 9 | 0.0 sacks, 0 interceptions, 1 fumble recovered | |
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| MLB | Fred Warner*+ | 26 | 4 | 17 | 2.0 sacks, 1 interception, 0 fumbles recovered | |
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| RLB | Dre Greenlaw | 25 | 3 | 15 | 0.0 sacks, 1 interception, 2 fumbles recovered | |
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| LCB | Deommodore Lenoir | 23 | 1 | 13 | 1.0 sacks, 1 interception, 0 fumbles recovered | |
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| RCB | Charvarius Ward | 26 | 4 | 17 | 0.0 sacks, 1 interception, 1 fumble recovered | |
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| SS | Talanoa Hufanga*+ | 22 | 1 | 17 | 2.0 sacks, 4 interceptions, 0 fumbles recovered | |
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| FS | Tashaun Gipson | 32 | 10 | 17 | 0.5 sacks, 5 interceptions, 0 fumbles recovered | |
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Roster