Massive Outlook issues since Monday: Not opening at all, freezing after 5 minutes, losing connection

EDIT: Finally got a client where the issue was constantly reproducible enough to get a Wireshark and ProcMon capture. Immediately noticed that while Outlook was in the middle of it's "not opening" phase, there were a **ton** of retransmits over IPv6 to Microsoft endpoints. For one example, 2603:1036:305:48ca::2 in Texas, which is our Exchange Online front door. Error on the event was "destination unreachable (no route to destination)".

Disabled IPv6 on the network adapter and their Outlook issues **immediately** went away.

I think somewhere there is a bad IPv6 routing issue.

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Since the beginning of this Monday, we've seen a pretty massive uptick in our environment of complaints about Outlook (another some other pieces of M365 Apps like Word, Excel, Teams) having issues. We are in Southeast US. For us, the most prevalent symptoms include:

* Outlook not opening at all

* Outlook freezing (going "not responding") after 5 minutes of usage

* Outlook will random lose connectivity and throw a red exclamation mark onto the taskbar icon

* Outlook not syncing messages until 20-30 minutes after the mailbox receives them

These issues persists across a reboot. We've already employed all manners of usual fix attempts (new profiles, clearing caches, etc) to no avail. The issue is reproducible when our EDR (Cisco Secure endpoint) is removed from a client. (First thing I suspected since this and other security clients broke Chrome from opening correctly starting last week)

Uninstalling the June 2023 Windows cumulative update does not affect the issue, and having M365 Apps on Current Channel or Monthly Enterprise Channel makes no difference for the symptoms.

Microsoft doesn't seem to be acknowledging any issues, and many of us are just plain stuck with royally pissed off users. This includes a few folks on Reddit that have been reporting this exact same thing since Monday as well:

https://old.reddit.com/r/Office365/comments/14f6g28/is_something_down

https://old.reddit.com/r/sysadmin/comments/14exlr6/office_issue

https://old.reddit.com/r/Office365/comments/14fbmrd/help_365_app_woes

Anyone else seeing this? I'm losing my mind here because we just get more and more reports with no end in sight...