Offense
| # | Name | Pos | Ht | Wt | Exp | College | Status |
| 61 | Matt Hennessy | C | 6'3" | 315 lbs | 6 | Temple | Active |
| 64 | Jake Brendel | C | 6'4" | 299 lbs | 8 | UCLA | Active |
| 66 | Drake Nugent | C | 6'1" | 300 lbs | 1 | Michigan | Practice Squad |
| 44 | Kyle Juszczyk | FB | 6'2" | 235 lbs | 13 | Harvard | Active |
| 75 | Connor Colby | G | 6'5" | 309 lbs | R | Iowa | Active |
| 62 | Austen Pleasants | OL | 6'7" | 330 lbs | 1 | Ohio | Active |
| 60 | Brandon Parker | OT | 6'8" | 320 lbs | 8 | North Carolina A&T | Practice Squad |
| 63 | Nick Zakelj | OT | 6'6" | 316 lbs | 4 | Fordham | Practice Squad |
| 67 | Isaac Alarcon | OT | 6'7" | 320 lbs | 1 | — | Practice Squad |
| 68 | Colton McKivitz | OT | 6'6" | 301 lbs | 6 | West Virginia | Active |
| 71 | Trent Williams | OT | 6'5" | 320 lbs | 16 | Oklahoma | Active |
| 74 | Spencer Burford | OT | 6'4" | 300 lbs | 4 | Texas-San Antonio | Active |
| 77 | Dominick Puni | OT | 6'5" | 313 lbs | 2 | Kansas | Active |
| 78 | Ben Bartch | OT | 6'6" | 315 lbs | 6 | St. John's (MN) | Reserve |
| — | Adrian Martinez | QB | 6'2" | 220 lbs | 1 | Kansas State | Practice Squad |
| 4 | Kurtis Rourke | QB | 6'4" | 221 lbs | R | Indiana | RSN |
| 10 | Mac Jones | QB | 6'3" | 220 lbs | 5 | Alabama | Active |
| 13 | Brock Purdy | QB | 6'1" | 220 lbs | 4 | Iowa State | Active |
| 3 | Brian Robinson | RB | 6'1" | 225 lbs | 2 | Alabama | Active |
| 23 | Christian McCaffrey | RB | 5'11" | 210 lbs | 9 | Stanford | Active |
| 29 | Jordan James | RB | 5'9" | 208 lbs | R | Oregon | Active |
| 31 | Isaac Guerendo | RB | 6'0" | 221 lbs | 2 | Louisville | Active |
| 32 | Patrick Taylor | RB | 6'1" | 217 lbs | 5 | Memphis | Reserve |
| 9 | Brayden Willis | TE | 6'4" | 240 lbs | 3 | Oklahoma | Active |
| 85 | George Kittle | TE | 6'4" | 250 lbs | 9 | Iowa | Reserve |
| — | Hayden Rucci | TE | 6'5" | 247 lbs | 1 | Wisconsin | Practice Squad |
| 88 | Jake Tonges | TE | 6'4" | 240 lbs | 3 | California | Active |
| 89 | Luke Farrell | TE | 6'5" | 250 lbs | 5 | Ohio State | Active |
| 1 | Ricky Pearsall | WR | 6'1" | 189 lbs | 2 | Florida | Active |
| 5 | Demarcus Robinson | WR | 6'1" | 203 lbs | 10 | Florida | Active |
| 6 | Skyy Moore | WR | 5'10" | 195 lbs | 4 | Western Michigan | Active |
| 7 | Malik Turner | WR | 6'2" | 202 lbs | 5 | Illinois | Practice Squad |
| 15 | Jauan Jennings | WR | 6'3" | 212 lbs | 5 | Tennessee | Active |
| 17 | Jordan Watkins | WR | 5'11" | 196 lbs | R | Mississippi | Active |
| 19 | Jacob Cowing | WR | 5'9" | 170 lbs | 2 | Arizona | Reserve |
| 81 | Trent Taylor | WR | 5'8" | 180 lbs | 7 | Louisiana Tech | Reserve |
| 84 | Kendrick Bourne | WR | 6'1" | 205 lbs | 9 | Eastern Washington | Active |
| 86 | Junior Bergen | WR | 5'9" | 184 lbs | R | Montana | Practice Squad |
Defense
| # | Name | Pos | Ht | Wt | Exp | College | Status |
| 2 | Deommodore Lenoir | CB | 5'10" | 200 lbs | 5 | Oregon | Active |
| 26 | Chase Lucas | CB | 5'11" | 184 lbs | 3 | Arizona State | Active |
| 28 | Darrell Luter Jr. | CB | 6'0" | 190 lbs | 3 | South Alabama | Active |
| 33 | Siran Neal | CB | 6'0" | 206 lbs | 8 | Jacksonville State | Active |
| 40 | Derrick Canteen | CB | 5'10" | 193 lbs | R | Cincinnati | Practice Squad |
| — | Eli Apple | CB | 6'1" | 203 lbs | 10 | Ohio State | Practice Squad |
| 49 | Jakob Robinson | CB | 5'10" | 181 lbs | R | BYU | Reserve |
| — | Renardo Green | CB | 6'0" | 186 lbs | 2 | Florida State | Active |
| — | Tre Tomlinson | CB | 5'9" | 177 lbs | 3 | TCU | Reserve |
| 20 | Upton Stout | CB | 5'9" | 182 lbs | R | Western Kentucky | Active |
| 47 | Bryce Huff | DE | 6'3" | 255 lbs | 6 | Memphis | Active |
| 51 | Robert Beal Jr. | DE | 6'4" | 250 lbs | 3 | Georgia | Active |
| 55 | Sebastian Valdez | DE | 6'3" | 301 lbs | R | Washington | Practice Squad |
| 56 | Tarron Jackson | DE | 6'2" | 254 lbs | 3 | Coastal Carolina | Reserve |
| 56 | Keion White | DE | 6'5" | 285 lbs | 3 | Georgia Tech | Active |
| 94 | Yetur Gross-Matos | DE | 6'5" | 265 lbs | 6 | Penn State | Active |
| 96 | Clelin Ferrell | DE | 6'4" | 265 lbs | 7 | Clemson | Active |
| 97 | Nick Bosa | DE | 6'4" | 266 lbs | 7 | Ohio State | Reserve |
| 98 | Mykel Williams | DE | 6'5" | 267 lbs | R | Georgia | Reserve |
| — | Will Bradley-King | DE | 6'4" | 265 lbs | 1 | Baylor | Practice Squad |
| 55 | Evan Anderson | DL | 6'3" | 326 lbs | 2 | Florida Atlantic | Practice Squad |
| 90 | Kevin Givens | DT | 6'1" | 285 lbs | 6 | Penn State | Active |
| 91 | Sam Okuayinonu | DT | 6'1" | 269 lbs | 3 | Maryland | Active |
| 92 | Jordan Elliott | DT | 6'4" | 302 lbs | 6 | Missouri | Active |
| 93 | Kalia Davis | DT | 6'2" | 310 lbs | 4 | UCF | Active |
| 95 | Alfred Collins | DT | 6'5" | 332 lbs | R | Texas | Active |
| 99 | CJ West | DT | 6'1" | 316 lbs | R | Indiana | Active |
| — | Andrew Farmer | LB | 6'4" | 250 lbs | 2 | Lane College | Practice Squad |
| — | Garret Wallow | LB | 6'2" | 230 lbs | 5 | TCU | Active |
| 41 | Jalen Graham | LB | 6'3" | 220 lbs | 3 | Purdue | Practice Squad |
| 45 | Nick Martin | LB | 5'11" | 221 lbs | R | Oklahoma State | Reserve |
| 48 | Tatum Bethune | LB | 6'0" | 230 lbs | 2 | Florida State | Reserve |
| 53 | Dee Winters | LB | 5'11" | 227 lbs | 3 | TCU | Active |
| 57 | Luke Gifford | LB | 6'3" | 242 lbs | 7 | Nebraska | Active |
| 59 | Curtis Robinson | LB | 6'3" | 235 lbs | 4 | Stanford | Active |
| — | Eric Kendricks | MLB | 6'0" | 232 lbs | 11 | UCLA | Active |
| 54 | Fred Warner | MLB | 6'3" | 230 lbs | 8 | BYU | Reserve |
| — | Kyzir White | OLB | 6'2" | 234 lbs | 8 | West Virginia | Practice Squad |
| — | Darrick Forrest | SAF | 5'11" | 200 lbs | 5 | Cincinnati | Practice Squad |
| 6 | Malik Mustapha | SAF | 5'10" | 206 lbs | 2 | Wake Forest | Active |
| 25 | Jason Pinnock | SAF | 6'0" | 200 lbs | 5 | Pittsburgh | Active |
| 27 | Ji'Ayir Brown | SAF | 5'11" | 202 lbs | 3 | Penn State | Active |
| 36 | Marques Sigle | SAF | 5'11" | 199 lbs | R | Kansas State | Active |
Special Teams
| # | Name | Pos | Ht | Wt | Exp | College | Status |
| 18 | Eddy Pineiro | K | 5'11" | 190 lbs | 8 | Florida | Active |
| 46 | Jon Weeks | LS | 5'10" | 242 lbs | 16 | Baylor | Active |
| 7 | Thomas Morstead | P | 6'4" | 225 lbs | 17 | SMU | Active |