Mail.app problems with Big Sur 11.0.1

Boot into Safe Mode (How to use safe mode on your Mac - Apple Support) by booting with the Shift key held down and and try opening Mail from there.  Reboot normally and try Mail again.

NOTE: Safe Mode boot can take up to 10 minutes as it's doing the following; 

• Verifies your startup disk and attempts to repair directory issues, if needed

• Loads only required kernel extensions (prevents 3rd party kernel/extensions from loading)

• Prevents Startup Items and Login Items from opening automatically

• Disables user-installed fonts 

• Deletes font caches, kernel cache, and other system cache files

I don't see any of the usual suspects in the report. It's quite clean. I see nothing that might be associated with the problems you're having with Mail.

Rerun Etrecheck and go to the Clean Up section to remove the items listed there.

💡Just had an idea: remove the mail icon from the Dock and go to the Applications folder and double click on the Mail app. See if that will open your Mail so you can see it.

If that works drag the Mail app from the Applications folder back into the Dock.

Log into another vanilla admin user account, Set up users, guests, and groups on Mac,  and see if the problem persists. (This tells us if the problem is limited to your user account or is system wide).

In your main account download and run Etrecheck. Etrecheck is a diagnostic tool that was developed by one of the most respected users here in the ASC and recommended by Apple Support  to provide a snapshot of the system and help identify the more obvious culprits that can adversely affect a Mac's performance.

Copy the report

and use the Additional Text button to include the report in your reply.

IMPORTANT:

Before running Etrecheck assign Full Disk Access to Etrecheck in the Etrecheck's Privacy preference pane so that it can get additional information from the Console and log files for the report:

Also click and read the About info to further permit full disk access.

Then we can examine the report and see if we can determine what might be causing the problem.

I had this problem too - Old Toad's suggestion worked for me - I removed the mail icon from my dock and opened it from the applications folder instead. Voila! Thanks so much - I spent the day trying to figure this out.

Regular mode. You can use the free version but do enable Full Disk access so we can get the full report.