Can´t connect to OneDrive with VPN enabled

The way I understand the OP, the error goes away if VPN is disabled, strongly indicating that the VPN is doing “something” that does not work. Most often this is caused by DNS problems on the VPN.

Also, I think this is a smoking gun:

With split tunneling enabled, netstat does not return anything.

Additionally, a Google search indicates multiple cases where the error message was related to DNS issues from the provider.
There are also some with Socket.Bind, but you can see in the trace that it is using Connect and not Bind.

The netstat non-return probably is seen below, i.e. it’s not simply a bare netstat:

and to me this suggests it didn’t connect, but it’s unclear why that would happen.
The netstat command should not be trying to slowly DNS-reverse the addresses.

With that clue, I found at least one where 0.0.0.0 was returned. I didn’t look much.

It can also happen on the remote address of a connect, per web search, and docs:

Windows Sockets Error Codes

Look at WSAEADDRNOTAVAIL

connect(3) - Linux man page

Look at EADDRNOTAVAIL

The DNS theory can maybe be tested (assuming you mean the remote side lookup):

(per Environment variables example in AutoUpdater)

C:\Program Files\Duplicati 2>set AUTOUPDATER_Duplicati_URLS=https://example.com/stable/latest.manifest

C:\Program Files\Duplicati 2>Duplicati.GUI.TrayIcon

About → Check for updates now

About …> Show log → Stored

Look at error. Mine seemingly resolved the remote, but (by its design) page isn’t there:

Jan 24, 2025 10:30 AM: Error in updater
System.Net.Http.HttpRequestException: Response status code does not indicate success: 404 (Not Found).
at System.Net.Http.HttpResponseMessage.EnsureSuccessStatusCode()
at Duplicati.Library.Utility.HttpClientExtensions.DownloadFile(HttpClient client, HttpRequestMessage request, String filename, Action`1 progressReportingAction, CancellationToken cancellationToken)
at Duplicati.Library.AutoUpdater.UpdaterManager.CheckForUpdate(ReleaseType channel)