| Player Name | Jersey No | Pos | HT | WT | Age | Exp | College |
| Brandon Aiyuk | 11 | WR | 6-0 | 200 | 24 | 3 | Arizona State |
| Azeez Al-Shaair | 51 | LB | 6-2 | 228 | 25 | 4 | Florida Atlantic |
| Arik Armstead | 91 | DL | 6-7 | 290 | 28 | 8 | Oregon |
| Aaron Banks | 65 | OL | 6-5 | 325 | 25 | 2 | Notre Dame |
| Nick Bosa | 97 | DL | 6-4 | 266 | 24 | 4 | Ohio State |
| Jake Brendel | 64 | OL | 6-4 | 299 | 29 | 6 | UCLA |
| Daniel Brunskill | 60 | OL | 6-5 | 300 | 28 | 4 | San Diego State |
| Spencer Burford | 74 | OL | 6-4 | 300 | 22 | R | Texas-San Antonio |
| Oren Burks | 48 | LB | 6-3 | 233 | 27 | 5 | Vanderbilt |
| Tyrion Davis-Price | 32 | RB | 6-1 | 219 | 21 | R | Louisiana State |
| Ross Dwelley | 82 | TE | 6-5 | 235 | 27 | 5 | San Diego |
| Samson Ebukam | 56 | DL | 6-3 | 245 | 27 | 6 | Eastern Washington |
| Demetrius Flannigan-Fowles | 45 | LB | 6-2 | 223 | 26 | 3 | Arizona |
| Jimmy Garoppolo | 10 | QB | 6-2 | 225 | 30 | 9 | Eastern Illinois |
| Kevin Givens | 90 | DL | 6-1 | 285 | 25 | 3 | Penn State |
| Robbie Gould | 9 | K | 6-0 | 190 | 39 | 18 | Penn State |
| Danny Gray | 86 | WR | 6-0 | 200 | 23 | R | Southern Methodist |
| Dre Greenlaw | 57 | LB | 6-0 | 230 | 25 | 4 | Arkansas |
| Talanoa Hufanga | 29 | S | 6-0 | 200 | 22 | 2 | Southern California |
| Kerry Hyder Jr. | 92 | DL | 6-2 | 275 | 31 | 7 | Texas Tech |
| Drake Jackson | 95 | DL | 6-4 | 273 | 21 | R | Southern California |
| Jauan Jennings | 15 | WR | 6-3 | 212 | 25 | 2 | Tennessee |
| Kyle Juszczyk | 44 | FB | 6-2 | 235 | 31 | 10 | Harvard |
| Javon Kinlaw | 99 | DT | 6-5 | 319 | 24 | 3 | South Carolina |
| George Kittle | 85 | TE | 6-4 | 250 | 28 | 6 | Iowa |
| Trey Lance | 5 | QB | 6-4 | 224 | 22 | 2 | North Dakota State |
| Deommodore Lenoir | 38 | DB | 5-10 | 200 | 22 | 2 | Oregon |
| Jordan Mason | 41 | RB | 5-11 | 223 | 23 | R | Georgia Tech |
| Ray-Ray McCloud III | 3 | WR | 5-9 | 190 | 25 | 5 | Clemson |
| Mike McGlinchey | 69 | T | 6-8 | 310 | 27 | 5 | Notre Dame |
| Colton McKivitz | 68 | OL | 6-6 | 301 | 26 | 3 | West Virginia |
| Elijah Mitchell | 25 | RB | 5-10 | 200 | 24 | 2 | Louisiana |
| Jaylon Moore | 76 | OL | 6-4 | 311 | 24 | 2 | Western Michigan |
| Tarvarius Moore | 33 | DB | 6-2 | 200 | 26 | 5 | Southern Mississippi |
| Emmanuel Moseley | 4 | CB | 5-11 | 190 | 26 | 5 | Tennessee |
| George Odum | 30 | S | 6-1 | 202 | 28 | 5 | Central Arkansas |
| Charles Omenihu | 94 | DL | 6-5 | 280 | 25 | 4 | Texas |
| Taybor Pepper | 46 | LS | 6-4 | 245 | 28 | 5 | Michigan State |
| Brock Purdy | 14 | QB | 6-1 | 220 | 22 | R | Iowa State |
| Hassan Ridgeway | 98 | DL | 6-3 | 305 | 27 | 7 | Texas |
| Curtis Robinson | 59 | LB | 6-3 | 235 | 24 | 2 | Stanford |
| Deebo Samuel | 19 | WR | 6-0 | 215 | 26 | 4 | South Carolina |
| Trey Sermon | 28 | RB | 6-0 | 215 | 23 | 2 | Ohio State |
| Ambry Thomas | 20 | CB | 6-0 | 190 | 22 | 2 | Michigan |
| Charvarius Ward | 35 | CB | 6-1 | 196 | 26 | 5 | Middle Tennessee State |
| Jimmie Ward | 1 | DB | 5-11 | 195 | 31 | 9 | Northern Illinois |
| Fred Warner | 54 | LB | 6-3 | 230 | 25 | 5 | Brigham Young |
| Trent Williams | 71 | T | 6-5 | 320 | 34 | 13 | Oklahoma |
| Jeff Wilson Jr. | 22 | RB | 6-0 | 213 | 26 | 5 | North Texas |
| Mitch Wishnowsky | 18 | P | 6-2 | 220 | 30 | 4 | Utah |
| Charlie Woerner | 89 | TE | 6-5 | 241 | 24 | 3 | Georgia |
| Samuel Womack III | 26 | CB | 5-10 | 189 | 23 | R | Toledo |
| Nick Zakelj | 63 | OL | 6-6 | 316 | 23 | R | Fordham |
| Maurice Hurst | 96 | DL | 6-2 | 291 | 27 | 5 | Michigan |
| Jordan Matthews | 88 | TE | 6-3 | 236 | 30 | 7 | Vanderbilt |
| Kalia Davis | 93 | DL | 6-2 | 310 | 23 | R | Central Florida |
| Jason Verrett | 2 | CB | 5-10 | 188 | 31 | 9 | Texas Christian |