While opening Mail, you may see this alert message even if your Home is not full:
"Mail cannot update your mailboxes because your home directory is full. You must free up space in your home folder before using Mail. Delete unneeded documents or move documents to another volume."
Verify that your home directory is not full
Choose Home from the Finder's Go menu and make sure the volume is not full by checking the space available on the drive.
If it is full you can free up space on the volume by removing (or archiving to a different volume) files and documents such as ones in your Documents folder and on your desktop.
If your home directory is not full
Once the issue is resolved, you can remove (delete) the "Envelope Index" file from your desktop
.