I needed some while to finally get Calibre working over SSL. Not sure this is something special to Ubuntu 18.10, but this was the problem:
I added as ssl paths:
/etc/letsencrypt/live/www.mydomain.com/fullcert.pem
/etc/letsencrypt/live/www.mydomain.com/privkey.pem
Starting the server always produced the error "permission denied". Tried to change access rights, but did help.
So I copied the certificates to /opt/calibre and changed the paths accordingly.
Then trying to start again an error, this time "file does not exist".
Needed a while to realize that in /etc/letsencrypt/live only symbolic links reside, not the file itself. And it looks like Calibre server cannot handle symbolic links for certificates.
The real files are in /etc/letsencrpyt/archive
After I copied those to /opt/calibre the service starts now without issue :-)
And I have a proper SSL connection outside my network.
So after I got this working from inside the Calibre app I created as well the calibre-server.service file so it starts with system boot using the same as above. And works as well.
As I'm very new to Linux/Ubuntu I might have done it in the first case wrong. But for other novice this might help.