Hi @Ben Wosjke ,
Given that 0 mailboxes are expected to be on prem, what is the impact, if any, of disabling the information store service ?
I've also tried searching a lot but cannot find any official document explicitly stating the impact on this scenario. But based on my understanding, since on-prem has no mailboxes at all, it won't have any impact.
From the article below, we can learn that Microsoft Exchange Information Store is used to manage the mailbox databases on the server. "If this service is stopped, mailbox databases on the server are unavailable." And according to the "Dependencies" field of the table, there's no other service that depends on the Information Store Service, which means disabling MSExchangeIS won't affect other Exchange services on the server.
Overview of Exchange services on Exchange servers
As regards to SMTP relay, as mentioned above, MSExchangeIS is used to manage mailbox databases, so it won't affect the mail flow given 0 mailbox is on prem. I tried testing in my on-prem environment as well using telnet and as can be seen from the message tracking log, storedrive is not involved for the sender side:
(The STOREDRIVER in the last line is because the recipient's mailbox is hosted on the on-prem server.)
When it comes to recipient management, actually you can manage recipients even if the Exchange sever is shut down. More details, you may refer to the document below:
Manage recipients in Exchange Hybrid environments using Management tools
Taken in the round, personally I don't think disabling MSExchangeIS will do any harm to your current environment. But to be on the safe side, you can start by testing it in non-working hours.
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