Transactions
| Date | Player | Pos | Transactions |
| 8/16 | Robert Nkemdiche | DT | cut |
| 8/15 | Darqueze Dennard | CB | cut |
| 8/15 | Josh Hokit | RB | cut |
| 8/15 | KeeSean Johnson | WR | cut |
| 8/15 | Tomasi Laulile | DT | cut |
| 8/12 | Leon O'Neal Jr. | S | cut |
| 8/12 | Leon O'Neal Jr. | S | off IR undisclosed |
| 8/11 | Leon O'Neal Jr. | S | on IR undisclosed |
| 8/10 | Ken Crawley | CB | signed/unrest FA One-year contract (through 2022) |
| 8/6 | Jordan Mills | T | signed/unrest FA One-year contract (through 2022) |
| 8/6 | Willie Snead IV | WR | signed One-year contract (through 2022) |
| 8/5 | Taysir Mack | WR | cut |
| 8/4 | Jordan Matthews | TE | on IR torn left ACL |
| 8/1 | Akeem Spence | DT | signed One-year contract (through 2022) |
| 8/1 | Maurice Hurst | DT | on IR torn biceps |
| 7/31 | Deebo Samuel | WR | re-signed Three-year extension (through 2025) |
| 7/29 | Tomasi Laulile | DT | signed |
| 7/27 | Dee Ford | DE | cut |
| 7/26 | Robert Nkemdiche | DT | signed/unrest FA One-year contract (through 2022) |
| 6/2 | Frank Gore | RB | signed One-day contract |
| 6/2 | Frank Gore | RB | retired |
| 6/2 | Alex Mack | C | retired |
| 6/2 | Spencer Burford | G | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Tariq Castro-Fields | CB | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Kalia Davis | DT | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Tyrion Davis-Price | RB | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Danny Gray | WR | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Drake Jackson | DE | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Brock Purdy | QB | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Samuel Womack III | CB | signed/draft choice Four-year contract (through 2025) |
| 6/2 | Nick Zakelj | G | signed/draft choice Four-year contract (through 2025) |
| 5/23 | Tyler Kroft | TE | signed/unrest FA One-year contract (through 2022) |
| 5/23 | Chris Slayton | DT | cut |
| 5/17 | Troy Fumagalli | TE | signed/unrest FA One-year contract (through 2022) |
| 5/17 | Garrett Walston | TE | cut |
| 5/13 | Kevin Atkins | DT | signed |
| 5/13 | Jeremiah Gemmel | LB | signed |
| 5/13 | Tayler Hawkins | S | signed |
| 5/13 | Qwuantrezz Knight | CB | signed |
| 5/13 | Taysir Mack | WR | signed |
| 5/13 | Tay Martin | WR | signed |
| 5/13 | Jordan Mason | RB | signed |
| 5/13 | Marcelino McCrary-Ball | LB | signed |
| 5/13 | Segun Olubi | LB | signed |
| 5/13 | Leon O'Neal Jr. | S | signed |
| 5/13 | Jason Poe | G | signed |
| 5/13 | Sam Schlueter | T | signed |
| 5/13 | Garrett Walston | TE | signed |
| 5/13 | Dohnovan West | C | signed |
| 5/13 | Connor Wedington | WR | cut |
| 5/2 | Jason Verrett | CB | re-signed/unrest FA One-year contract (through 2022) |
| 4/25 | Nick Bosa | DE | team exercises option Fifth-year option on rookie contract |
| 4/25 | Azeez Al-Shaair | LB | re-signed/rest FA One-year contract (through 2022) |
| 4/19 | Daniel Brunskill | T | re-signed/rest FA One-year contract (through 2022) |
| 4/19 | Jauan Jennings | WR | re-signed/excl. FA One-year contract (through 2022) |
| 4/14 | Kemoko Turay | DE | signed/unrest FA One-year contract (through 2022) |
| 4/11 | Marcus Johnson | WR | signed/unrest FA One-year contract (through 2022) |
| 4/11 | Malik Turner | WR | signed/unrest FA One-year contract (through 2022) |
| 4/11 | Maurice Hurst | DT | cut |
| 4/11 | Maurice Hurst | DT | signed One-year contract (through 2022) |
| 3/29 | Jeff Wilson Jr. | RB | re-signed/unrest FA One-year contract (through 2022) |
| 3/28 | Ross Dwelley | TE | re-signed/unrest FA One-year contract (through 2022) |
| 3/25 | Darqueze Dennard | CB | signed One-year contract (through 2022) |
| 3/24 | Kerry Hyder Jr. | DE | signed One-year contract (through 2022) |
| 3/24 | Dontae Johnson | CB | re-signed/unrest FA One-year contract (through 2022) |
| 3/23 | Jordan Willis | DE | re-signed/unrest FA One-year contract (through 2022) |
| 3/22 | George Odum | S | signed/unrest FA Three-year contract (through 2024) |
| 3/22 | Ray-Ray McCloud III | WR | signed/unrest FA One-year contract (through 2022) |
| 3/21 | Hassan Ridgeway | DT | signed/unrest FA One-year contract (through 2022) |
| 3/17 | Oren Burks | LB | signed/unrest FA Two-year contract (through 2023) |
| 3/16 | Charvarius Ward | CB | signed/unrest FA Three-year contract (through 2024) |
| 3/16 | Trenton Cannon | RB | Declared Free Agent |
| 3/16 | Laken Tomlinson | G | Declared Free Agent |
| 3/16 | Travis Benjamin | WR | Declared Free Agent |
| 3/16 | Tom Compton | G | Declared Free Agent |
| 3/16 | Ross Dwelley | TE | Declared Free Agent |
| 3/16 | Marcell Harris | S | Declared Free Agent |
| 3/16 | Richie James Jr. | WR | Declared Free Agent |
| 3/16 | Dontae Johnson | CB | Declared Free Agent |
| 3/16 | D.J. Jones | DT | Declared Free Agent |
| 3/16 | Arden Key | DE | Declared Free Agent |
| 3/16 | Raheem Mostert | RB | Declared Free Agent |
| 3/16 | Josh Norman | CB | Declared Free Agent |
| 3/16 | Mohamed Sanu Sr. | WR | Declared Free Agent |
| 3/16 | Trent Sherfield | WR | Declared Free Agent |
| 3/16 | Jaquiski Tartt | S | Declared Free Agent |
| 3/16 | Jason Verrett | CB | Declared Free Agent |
| 3/16 | K'Waun Williams | CB | Declared Free Agent |
| 3/16 | Jordan Willis | DE | Declared Free Agent |
| 3/16 | Tavon Wilson | S | Declared Free Agent |
| 3/16 | Jeff Wilson Jr. | RB | Declared Free Agent |
| 3/16 | Azeez Al-Shaair | LB | Restricted Free Agent |
| 3/16 | Daniel Brunskill | T | Restricted Free Agent |
| 3/16 | Kentavius Street | DT | Declared Free Agent |
| 3/11 | Demetrius Flannigan-Fowles | LB | re-signed/excl. FA One-year extension (through 2022) |
| 3/10 | Kevin Givens | DT | re-signed One-year extension (through 2022) |
| 3/10 | JaMycal Hasty | RB | re-signed One-year extension (through 2022) |
| 3/10 | Maurice Hurst | DT | re-signed One-year extension (through 2022) |
| 3/10 | Colton McKivitz | T | re-signed One-year extension (through 2022) |
| 3/10 | Nate Sudfeld | QB | signed |
| 3/9 | Jake Brendel | C | re-signed One-year extension (through 2022) |
| 3/8 | Keaton Sutherland | G | signed |
| 2/15 | Tarvarius Moore | S | Activated from PUPL |
Last updated Aug. 18, 1:03 A.M. ET
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