Hi Jeff,
I have some questions for you:
1. Are you saving just to the server itself or to Sharepoint?
2. Are you saving to a NAS device?
3. Are you running any data loss prevention software or other scanning software?
If yes, stop those services on the server AND the client and test for improvement.
4. If you have a group of users that are able to reproduce the issue, is it specific to any particular files that they are using?
4a. Are those files shared by just being in a folder everyone has access to or are they truly [shared] within the Excel UI so that multiple users can make changes at the same time?
5. Are the users truly and physically 'saving' (file > save or ctrl+s) their changes or are they using the just assuming that the auto-recover feature ran and saved their changes?
6. Do you have all updates applied to all products involved?
7. Does it happen only on a particular server? Try moving the files to another server and testing.
8. Is there anything similar about the files? ie. do they all contain VBA, are they only on one particular server, or they all one specific file type (.xls, .xlsx, etc), are they only files that one particular department of users use.... if yes, then do
they use any other applications with these files or run any additional add-ins within the Excel application?
9. Will it happen with NEW file?
Additionally, you could try capturing a Process Monitor trace to see if anything interferes on the client side when saving, but simultaneous Network Monitor traces may also help show you any issues with network communication or interference.
Process Monitor v2.96
http://technet.microsoft.com/en-us/sysinternals/bb896645
Information about Network Monitor 3
http://support.microsoft.com/kb/933741
Your scenario is not a popular one, so a case with Microsoft support may be better suited to help resolve your issue but if you can provide more feedback we may be able to find the root cause before taking that step.
Thanks,
Amber