Odd network playback problem

I’m using a VPN in split tunnel mode on the computer that’s running my Plex server which is setup within Infuse.
When I try and play a show in Infuse I always get a service unavailable error message.
It’s easy to blame the VPN software for this except that Infuse is the only application I’ve encounted this with so far, other apps, including Plex, work ok.