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This problem most commonly occurs when SQL Mail is configured to use internet protocols for message delivery. For Microsoft Outlook 2002 and later versions, the outgoing mail spooler is part of the process space for Outlook. Because of this change in the way Outlook functions, SQL Mail cannot deliver mail using SMTP when the Outlook client is not running. However, when the Outlook client is running, SQL Mail may not be able to open the mailbox files for the mail profile.
To resolve the problem, update your applications to use Database Mail.