The NFL announced that they will be releasing the 2021 schedule after the draft, a timeline they also followed in 2020
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| Detroit Lions vs Los Angeles Chargers | |
| Type: Point Spread - Status: OPEN | |
| Detroit Lions | -105 |
| Los Angeles Chargers | -115 |
| AFC Conference vs NFC Conference | |
| Type: Moneyline - Status: OPEN | |
| NFC Conference | -105 |
| AFC Conference | -115 |
| AFC Conference vs NFC Conference | |
| Type: Moneyline - Status: OPEN | |
| AFC Conference | -115 |
| NFC Conference | -105 |