Hi Doug,
I don't know exactly how the Excel Lookup plugin is coded, but generally, trying to open an Excel file that is already open will cause issues. Not just with this plugin either, even ODBC connections to Excel files will fail, so I don't know if it's even possible.
Even if it was, I don't think our devs will change the plugin anytime soon since it has been working this way for several years now, and there hasn't been any complaints about this until now. In the end, the cause of this is the bad practice of not closing documents. So instead of changing the software to accomodate a bad practice, I believe the best solution is to fix the bad practice, and have the users properly close their documents when they are done editing them.
Regards,
Raphaël Lalonde Lefebvre