| Name | Pos | Team | Age | Injured List |
|---|---|---|---|---|
| Eric Haase | C (OF,DH) | Det | 28 | |
| Daulton Varsho | C (OF) | Ari | 25 | |
| Mike Zunino | C | TB | 30 | |
| Anthony Rizzo | 1B | NYA | 32 | |
| Rowdy Tellez | 1B (DH) | Mil | 26 | September 12, 2021:10 Day IL-Right patella strain |
| Jake Cronenworth | 2B (1B,SS) | SD | 27 | |
| Garrett Hampson | 2B (SS,OF) | Col | 26 | |
| Xander Bogaerts | SS (DH) | Bos | 28 | |
| J.P. Crawford | SS | Sea | 26 | |
| Nolan Arenado | 3B | StL | 30 | |
| Jeimer Candelario | 3B (DH) | Det | 27 | |
| Bobby Dalbec | 3B (1B) | Bos | 26 | |
| Josh Donaldson | 3B (DH) | Min | 35 | |
| Akil Baddoo | OF (DH) | Det | 23 | |
| Michael Brantley | OF (DH) | Hou | 34 | September 12, 2021:10 Day IL-Right knee soreness |
| Byron Buxton | OF | Min | 27 | |
| Dylan Carlson | OF | StL | 22 | |
| Ian Happ | OF (2B) | ChN | 27 | |
| Austin Meadows | OF (DH) | TB | 26 | |
| Julio Rodriguez | OF | Sea | 20 | |
| Kyle Schwarber | OF (1B,DH) | Bos | 28 | |
| Ian Anderson | SP | Atl | 23 | |
| Aaron Civale | SP | Cle | 26 | |
| Marco Gonzales | SP | Sea | 29 | |
| Tanner Houck | SP (RP) | Bos | 25 | |
| Merrill Kelly | SP | Ari | 32 | |
| Eric Lauer | SP (RP) | Mil | 26 | |
| Daniel Lynch | SP | KC | 24 | |
| Matt Manning | SP | Det | 23 | |
| Wade Miley | SP | Cin | 34 | September 22, 2021:10 Day IL-Neck strain |
| Casey Mize | SP | Det | 24 | |
| Wily Peralta | SP | Det | 32 | |
| Tarik Skubal | SP (RP) | Det | 24 | |
| Jose Urquidy | SP | Hou | 26 |