*CSD Comunicaciones 1-1 Colorado Rapids
| 24.02.2022 | Colorado Rapids | 1-0/p.3-4 | CSD Comunicaciones | |
| 18.02.2022 | CSD Comunicaciones | 1-0 | Colorado Rapids | |
Deportivo Guastatoya 0-3 Club León *
| 23.02.2022 | Club León | 1-0 | Deportivo Guastatoya | |
| 17.02.2022 | Deportivo Guastatoya | 0-2 | Club León | |
Cavaly AS 0-3 New England Revs *
| 23.02.2022 | New England Revs | CANC | Cavaly AS | |
| 18.02.2022 | Cavaly AS | 0-3 W.O. | New England Revs | |
Santos Guápiles 0-6 New York City FC *
| 24.02.2022 | New York City FC | 4-0 | Santos Guápiles | |
| 16.02.2022 | Santos Guápiles | 0-2 | New York City FC | |
Santos Laguna 1-3 CF Montréal *
| 24.02.2022 | CF Montréal | 3-0 | Santos Laguna | |
| 16.02.2022 | Santos Laguna | 1-0 | CF Montréal | |
Saprissa 3-6 UNAM Pumas *
| 24.02.2022 | UNAM Pumas | 4-1 | Saprissa | |
| 17.02.2022 | Saprissa | 2-2 | UNAM Pumas | |
CD Motagua 0-5 Seattle Sounders *
| 25.02.2022 | Seattle Sounders | 5-0 | CD Motagua | |
| 18.02.2022 | CD Motagua | 0-0 | Seattle Sounders | |