| Offensive Starters | | | | | |
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| QB | Brock Purdy* | 24 | 1 | 16 | 308 for 444, 4,280 yards, 31 td, 11 int, & 39 rushes for 144 yards and 2 td | |
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| RB | Christian McCaffrey*+ | 27 | 6 | 16 | 272 rushes for 1,459 yards, 14 td, & 67 catches for 564 yards and 7 td | |
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| FB | Kyle Juszczyk*+ | 32 | 10 | 16 | 5 rushes for 6 yards, 0 td, & 14 catches for 119 yards and 2 td | |
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| WR | Brandon Aiyuk | 25 | 3 | 16 | 75 catches for 1,342 yards, 7 td | |
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| WR | Deebo Samuel | 27 | 4 | 15 | 60 catches for 892 yards, 7 td, & 37 rushes for 225 yards and 5 td | |
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| TE | George Kittle*+ | 30 | 6 | 16 | 65 catches for 1,020 yards, 6 td, & 1 rush for 2 yards and 0 td | |
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| LT | Trent Williams*+ | 35 | 13 | 15 | | |
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| LG | Aaron Banks | 26 | 2 | 14 | | |
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| C | Jake Brendel | 31 | 7 | 17 | | |
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| RG | Spencer Burford | 23 | 1 | 13 | | |
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| RT | Colton McKivitz | 27 | 3 | 17 | | |
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| Defensive Starters | | | | | |
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| LDE | Clelin Ferrell | 26 | 4 | 17 | 3.5 sacks, 0 interceptions, 1 fumble recovered | |
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| LDT | Arik Armstead | 30 | 8 | 12 | 5.0 sacks, 0 interceptions, 0 fumbles recovered | |
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| RDT | Javon Hargrave* | 30 | 7 | 16 | 7.0 sacks, 0 interceptions, 0 fumbles recovered | |
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| RDE | Nick Bosa* | 26 | 4 | 17 | 10.5 sacks, 0 interceptions, 1 fumble recovered | |
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| LLB | Ambry Thomas | 24 | 2 | 6 | 0.0 sacks, 1 interception, 1 fumble recovered | |
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| MLB | Fred Warner*+ | 27 | 5 | 17 | 2.5 sacks, 4 interceptions, 0 fumbles recovered | |
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| RLB | Dre Greenlaw | 26 | 4 | 15 | 1.5 sacks, 0 interceptions, 0 fumbles recovered | |
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| LCB | Charvarius Ward* | 27 | 5 | 17 | 0.0 sacks, 5 interceptions, 0 fumbles recovered | |
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| RCB | Deommodore Lenoir | 24 | 2 | 17 | 0.0 sacks, 3 interceptions, 0 fumbles recovered | |
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| SS | Talanoa Hufanga | 24 | 2 | 10 | 0.0 sacks, 3 interceptions, 0 fumbles recovered | |
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| FS | Tashaun Gipson | 33 | 11 | 16 | 1.0 sacks, 1 interception, 0 fumbles recovered | |
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Roster