How ready is Fedora to be run with IPv6 only?

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I have successfully tested Fedora 33 with IPv4 disabled:

sudo nmcli connection modify id CON_NAME ipv4.method disabled
sudo systemctl reboot

The core system can work relying only on IPv6 connectivity, that includes:

  • kernel, systemd, DNF, NetworkManager and most CLI tools.
  • GNOME and most desktop apps.

The only problems you may have are related to specific apps that depend on IPv4 domains.
E.g. the GNOME Shell OpenWeather extension fails due to its service not available over IPv6.

Although you shouldn’t disable IPv4 explicitly since there are still many IPv4-only sites.

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