Summary and Info:
Since upgrading from pacman 5.0.2-3 to pacman 5.1.0-2, all requests started failing. Invoking "pacman -Sy" for example would only perform requests to "/core/os/x86_64 " (note the odd space at the end).

It turns out that my custom mirror configuration with comments were parsed differently due to  FS#48702 :
Server = http://10.0.2.2:8080/$repo/os/$arch # comment here
It used to be parsed as "http://10.0.2.2:8080/$repo/os/$arch", but is now parsed as "http://10.0.2.2:8080/$repo/os/$arch # comment here". Due to how URLs work, everything appended after that is ignored.

This was not entirely obvious given that bash scripts and makepkg config accept comments like that just fine. If this is disallowed, consider updating pacman.conf(5).

https://xkcd.com/1172/