Depth Chart
| Offense | |||
| Position | |||
| Left Tackle | Trent Williams | ||
| Left Guard | Laken Tomlinson | Colton McKivitz | |
| Center | Alex Mack | Jake Brendel | |
| Right Guard | Daniel Brunskill | Aaron Banks | |
| Right Tackle | Jaylon Moore | Tom Compton | |
| Wide Receiver | Deebo Samuel | Travis Benjamin | Jauan Jennings |
| Wide Receiver | Brandon Aiyuk | Trent Sherfield | River Cracraft |
| Running Back | Eli Mitchell | Jeff Wilson Jr. | JaMycal Hasty |
| Tight End | George Kittle | Ross Dwelley | Charlie Woerner |
| Quarterback | Jimmy Garoppolo | Trey Lance | |
| Defense | |||
| Position | |||
| Left Defensive End | Nick Bosa | Jordan Willis | Charles Omenihu |
| Left Defensive Tackle | Arik Armstead | Maurice Hurst | |
| Right Defensive Tackle | D.J. Jones | Kentavius Street | Kevin Givens |
| Right Defensive End | Samson Ebukam | Arden Key | |
| Strong Linebacker | Marcell Harris | ||
| Middle Linebacker | Fred Warner | Demetrius Flannigan-Fowles | |
| Weak Linebacker | Dre Greenlaw | Azeez Al-Shaair | |
| Left Cornerback | Ambry Thomas | K'Waun Williams | Dontae Johnson |
| Right Cornerback | Josh Norman | Deommodore Lenoir | Emmanuel Moseley |
| Strong Safety | Jaquiski Tartt | Talanoa Hufanga | |
| Free Safety | Jimmie Ward | Dontae Johnson | Jarrod Wilson |
| Special Teams | |||
| Position | |||
| Kicker | Robbie Gould | ||
| Kick-Offs | Robbie Gould | ||
| Punter | Mitch Wishnowsky | ||
| Kick Returner | Eli Mitchell | Ambry Thomas | River Cracraft |
| Punt Returner | Brandon Aiyuk | River Cracraft | |
| Holder | Mitch Wishnowsky | ||
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