| Name | Position | Ht. | Wt. | School | |
| Kevin Atkins | DL | 6-2 | 307 | Fresno State | |
| Jeremiah Gemmel | LB | 6-1 | 225 | North Carolina | |
| Tayler Hawkins | S | 6-1 | 205 | San Diego State | |
| Qwuantrezz Knight | CB | 6-0 | 199 | UCLA | |
| Taysir Mack | WR | 6-2 | 190 | Pittsburgh | |
| Tay Martin | WR | 6-3 | 185 | Oklahoma State | |
| Jordan Mason | RB | 5-11 | 223 | Georgia Tech | |
| Marcelino McCrary-Ball | LB | 6-0 | 214 | Indiana | |
| Segun Olubi | LB | 6-2 | 220 | San Diego State | |
| Leon O'Neal Jr. | S | 6-1 | 210 | Texas A&M | |
| Jason Poe | OL | 6-1 | 300 | Mercer | |
| Sam Schlueter | OL | 6-6 | 309 | Minnesota | |
| Garrett Walston | TE | 6-4 | 245 | North Carolina | |
| Dohnovan West | OL | 6-4 | 300 | Arizona State | |
The 49ers initially signed Wedington to the practice squad on October 5, 2021. They had signed the receiver to a reserve/future contract on February 2.
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