I came across from here https://bugs.launchpad.net/ubuntu/+source/apache2/+bug/1939678 After Update from Ubuntu 18.04 apache2 2.4.29 to Ubuntu 20.04 apache2 2.4.41 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - To Reproduce i create two new Virtual Box VMs on my local Machine and compile apach2 from the sources 2.4.38 -> 2.4.51 ------------- |Bastian Host | |Apache Proxy | -----------> LB Apache Balancer Manger ------------- Debian 11 -> Bastion Host (Proxy) / 192.168.56.70 Ubuntu 20.04 -> LB Manager / 192.168.56.170 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - I use the Proxy as Bastion Host to reache several LB Manager from one Point. Debian 11 Proxy strip down config for reproduce the issue. :~# apt-get install apache2 ~# vim /etc/apache2/sites-enabled/000-default.conf [...] ProxyPass http://192.168.56.170:81/balancer-manager ProxyPassReverse http://192.168.56.170:81/balancer-manager SetOutputFilter INFLATE;SUBSTITUTE Substitute "s|http://192.168.56.70:81|http://192.168.56.170|i" [...] :~# a2enmod proxy_http substitute :~# systemctl restart apache2 - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - - Second VM with Ubuntu 20.04 for testing and reproduction. I compile apache from the sources. I Start with apache 2.4.38 wget http://archive.apache.org/dist/httpd/httpd-2.4.38.tar.gz configure / make / make install :~# vim /usr/local/apache2/conf/httpd.conf ServerRoot "/usr/local/apache2" ServerName "localhost" ServerAdmin