Offensive Positions
| POS | Starter | Second | Third+ |
|---|---|---|---|
| Quarterback | J. Garoppolo Jimmy Garoppolo | N. Mullens Nick Mullens | |
| Running Back | R. Mostert Raheem Mostert | T. Coleman Tevin Coleman | |
| Fullback | K. Juszczyk Kyle Juszczyk | — | — |
| Wide Receiver | D. Samuel Deebo Samuel | E. Sanders Emmanuel Sanders | |
| Tight End | G. Kittle George Kittle | R. Dwelley Ross Dwelley | |
| Left Tackle | J. Staley Joe Staley | J. Skule Justin Skule | — |
| Left Guard | L. Tomlinson Laken Tomlinson | — | — |
| Center | B. Garland Ben Garland | — | — |
| Right Tackle | M. McGlinchey Mike McGlinchey | D. Brunskill Daniel Brunskill | — |
Defensive Positions
| POS | Starter | Second | Third+ |
|---|---|---|---|
| Left Defensive End | N. Bosa Nick Bosa | D. Ford Dee Ford | |
| Right Defensive End | A. Armstead Arik Armstead | R. Blair Ronald Blair | |
| Left Defensive Tackle | S. Thomas Solomon Thomas | D. Jones D.J. Jones | — |
| Right Defensive Tackle | K. Street Kentavius Street | J. Taylor Jullian Taylor | |
| Strongside Linebacker | K. Alexander Kwon Alexander | M. Nzeocha Mark Nzeocha | |
| Middle Linebacker | F. Warner Fred Warner | J. Walker Joe Walker | — |
| Weakside Linebacker | D. Greenlaw Dre Greenlaw | E. Lee Elijah Lee | — |
| Right Cornerback | E. Moseley Emmanuel Moseley | A. Witherspoon Ahkello Witherspoon | |
| Left Cornerback | R. Sherman Richard Sherman | K. Williams K'Waun Williams | |
| Strong Safety | J. Tartt Jaquiski Tartt | M. Harris Marcell Harris | |
| Free Safety | J. Ward Jimmie Ward | T. Moore Tarvarius Moore |
Special Teams Positions
| POS | Starter | Second | Third+ |
|---|---|---|---|
| Punter | M. Wishnowsky Mitch Wishnowsky | — | — |
| Kicker | R. Gould Robbie Gould | — | — |
| Long Snapper | K. Nelson Kyle Nelson | — | — |
| Holder | M. Wishnowsky Mitch Wishnowsky | — | — |
| Punt Returner | R. James Richie James | D. Pettis Dante Pettis | |
| Kick Returner | R. James Richie James | — |