When creating a new site, a valid certificate was issued but when expiring they where never renewed. Investigating /etc/letsencrypt directories was missing the usual subfolders, like live for example.
It turned out the server had both acme.sh and certbot installed. The solution was to remove certbot. Investigate if the directory /root/.acme.sh exists and it’s contents.
apt remove certbot
Then in Ispconfig go to Tools -> Sync, select Web sites and the server you just removed.