Hello, @Lior Tomer,
Welcome to the Microsoft Q&A platform!
Based on your description, I understand that any message you sent to more than one recipient has received a "452 4.5.3 Too many recipients (AS780090)" error for all recipients except the first one since last Friday.
To find out more precisely what the problem is, I would like to ask you some questions:
- Have you recently changed your system settings?
- What is the approximate number of recipients of your email?
- Can you send emails to internal recipients normally without using the SMTP connector?
At the same time, you can use the Get-OutboundConnector command in PowerShell to view configuration information for the outbound connector.
In order to whitelist the domains and email addresses you need, please follow the steps below in Microsoft Defender.
About how to use PowerShell for the same purpose, you can refer to this document: Allow or block email using the Tenant Allow/Block List - Microsoft Defender for Office 365 | Microsoft Learn.
Regarding the encrypted inbound SMTP connector that your O365 tenant creates for you, Office 365 applies anti-spam and anti-abuse measures even when using an encrypted inbound SMTP connector. Encryption ensures data privacy in transit, but does not bypass other security protocols.
In order to solve your problem more effectively, I hope you can take the time to reply to me! Accept the answer if the information helped you. Thank you for your support and understanding.
Best Wishes,
Alex Zhang