Offense
| NUMBER | PLAYER | POSITION | HT | WT | DOB | AGE | EXP | COLLEGE |
| 10 | Jimmy Garoppolo | QB | 6-2 | 225 | 11/2/1991 | 30 | 9 | E. Illinois |
| 5 | Trey Lance | QB | 6-4 | 224 | 5/9/2000 | 22 | 2 | N. Dakota St. |
| 14 | Brock Purdy | QB | 6-1 | 220 | 12/27/1999 | 22 | R | Iowa St. |
| 32 | Tyrion Davis-Price | RB | 6-1 | 219 | 10/23/2000 | 21 | R | LSU |
| 41 | Jordan Mason | RB | 5-11 | 223 | 5/24/1999 | 23 | R | Georgia Tech |
| 22 | Jeff Wilson | RB | 6-0 | 213 | 11/16/1995 | 26 | 5 | North Texas |
| 44 | Kyle Juszczyk | FB | 6-2 | 235 | 4/23/1991 | 31 | 10 | Harvard |
| 11 | Brandon Aiyuk | WR | 6-0 | 200 | 3/17/1998 | 24 | 3 | Arizona St. |
| 86 | Danny Gray | WR | 6-0 | 200 | 4/1/1999 | 23 | R | SMU |
| 15 | Jauan Jennings | WR | 6-3 | 212 | 7/10/1997 | 25 | 2 | Tennessee |
| 3 | Ray-Ray McCloud | WR | 5-9 | 190 | 10/15/1996 | 25 | 5 | Clemson |
| 19 | Deebo Samuel | WR | 6-0 | 215 | 1/15/1996 | 26 | 4 | South Carolina |
| 82 | Ross Dwelley | TE | 6-5 | 235 | 1/26/1995 | 27 | 5 | San Diego |
| 85 | George Kittle | TE | 6-4 | 250 | 10/9/1993 | 28 | 6 | Iowa |
| 47 | Tyler Kroft | TE | 6-6 | 252 | 10/15/1992 | 29 | 8 | Rutgers |
| 89 | Charlie Woerner | TE | 6-5 | 241 | 10/16/1997 | 24 | 3 | Georgia |
| 64 | Jake Brendel | C | 6-4 | 299 | 9/10/1992 | 30 | 6 | UCLA |
| 60 | Daniel Brunskill | OT | 6-5 | 300 | 1/27/1994 | 28 | 4 | San Diego St. |
| 74 | Spencer Burford | OT | 6-4 | 300 | 7/19/2000 | 22 | R | Texas-San Antonio |
| 69 | Mike McGlinchey | OT | 6-8 | 310 | 1/12/1995 | 27 | 5 | Notre Dame |
| 68 | Colton McKivitz | OT | 6-6 | 301 | 8/9/1996 | 26 | 3 | West Virginia |
| 76 | Jaylon Moore | OT | 6-4 | 311 | 1/9/1998 | 24 | 2 | W. Michigan |
| 71 | Trent Williams | OT | 6-5 | 320 | 7/19/1988 | 34 | 13 | Oklahoma |
| 63 | Nick Zakelj | OT | 6-6 | 316 | 6/22/1999 | 23 | R | Fordham |
| 61 | Blake Hance | OG | 6-6 | 310 | 1/11/1996 | 26 | 2 | Northwestern |
Defense
| NUMBER | PLAYER | POSITION | HT | WT | DOB | AGE | EXP | COLLEGE |
| 91 | Arik Armstead | DE | 6-7 | 290 | 11/15/1993 | 28 | 8 | Oregon |
| 97 | Nick Bosa | DE | 6-4 | 266 | 10/23/1997 | 24 | 4 | Ohio St. |
| 56 | Samson Ebukam | DE | 6-3 | 245 | 5/9/1995 | 27 | 6 | E. Washington |
| 92 | Kerry Hyder | DE | 6-2 | 275 | 5/2/1991 | 31 | 7 | Texas Tech |
| 95 | Drake Jackson | DE | 6-4 | 273 | 4/12/2001 | 21 | R | USC |
| 94 | Charles Omenihu | DE | 6-5 | 280 | 8/20/1997 | 25 | 4 | Texas |
| 75 | Jordan Willis | DE | 6-4 | 270 | 5/2/1995 | 27 | 6 | Kansas St. |
| 90 | Kevin Givens | DT | 6-1 | 285 | 3/1/1997 | 25 | 3 | Penn St. |
| 99 | Javon Kinlaw | DT | 6-5 | 319 | 10/3/1997 | 24 | 3 | South Carolina |
| 98 | Hassan Ridgeway | DT | 6-3 | 305 | 11/2/1994 | 27 | 7 | Texas |
| 48 | Oren Burks | ILB | 6-3 | 233 | 3/21/1995 | 27 | 5 | Vanderbilt |
| 54 | Fred Warner | MLB | 6-3 | 230 | 11/19/1996 | 25 | 5 | BYU |
| 51 | Azeez Al-Shaair | LB | 6-2 | 228 | 8/4/1997 | 25 | 4 | FAU |
| 45 | Demetrius Flannigan-Fowles | LB | 6-2 | 223 | 9/4/1996 | 26 | 3 | Arizona |
| 57 | Dre Greenlaw | LB | 6-0 | 230 | 5/25/1997 | 25 | 4 | Arkansas |
| 38 | Deommodore Lenoir | CB | 5-10 | 200 | 10/6/1999 | 22 | 2 | Oregon |
| 20 | Ambry Thomas | CB | 6-0 | 190 | 9/9/1999 | 23 | 2 | Michigan |
| 35 | Charvarius Ward | CB | 6-1 | 196 | 5/16/1996 | 26 | 5 | Middle Tenn. |
| 26 | Samuel Womack | CB | 5-10 | 189 | 7/7/1999 | 23 | R | Toledo |
| 33 | Tarvarius Moore | DB | 6-2 | 200 | 8/16/1996 | 26 | 5 | So. Miss |
| 4 | Emmanuel Moseley | DB | 5-11 | 190 | 3/25/1996 | 26 | 5 | Tennessee |
| 30 | George Odum | DB | 6-1 | 202 | 11/3/1993 | 28 | 5 | Cent. Ark. |
| 29 | Talanoa Hufanga | SAF | 6-0 | 200 | 2/1/2000 | 22 | 2 | USC |
| 31 | Tashaun Gipson | FS | 6-1 | 207 | 8/7/1990 | 32 | 11 | Wyoming |
Special Teams
| NUMBER | PLAYER | POSITION | HT | WT | DOB (AGE) | AGE | EXP | COLLEGE |
| 9 | Robbie Gould | K | 6-0 | 190 | 12/6/1982 | 39 | 18 | Penn St. |
| 18 | Mitch Wishnowsky | P | 6-2 | 220 | 3/2/1992 | 30 | 4 | Utah |
| 46 | Taybor Pepper | LS | 6-4 | 245 | 5/28/1994 | 28 | 5 | Michigan St. |
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