What should I check in my server to be ready for sending newsletters to thousands of my site users?

Thousands of mails in the same time is vague. Maybe you could clarify a bit more. Thousands of emails a minute, a hour, or spread out over a day?

To answer you question though, I'd keep an eye on the performance monitor for the normal items such as RAM, CPU, Disk I/O.

Slightly off from the focus of your question, I would also make sure that the IP you are sending from doesn't send other emails. Even if you are sending to a 100% legit list of email addresses you still risk being black listed if too many people believe your newsletter to be spam.

I'm looking at your question from a slightly different viewpoint. One of our servers is a P4, 2GB server running SBS2003 (Exchange), and that will diligently send 3-4 thousand emails in an afternoon. The emails simply get queued and delivered in turn.

Technical/configuration tasks:

• You need a reverse DNS entry for the IP address that the mailserver sends from.
• Installing DKIM will help with delivery to some ISPs including Yahoo.
• Adding an SPF record will also help (another user on serverfault says this counts against you - he works for an anti-spam company and says they find spammers are more likely to use a correctly-defined SPF record than non-spammers although gmail/Hotmail still use SPF amongst others)

Then you need to set up some processes:

• Get signed up to AOL, Yahoo, etc's feedback loops and build in a system for removing any email where the user hit "report spam". The number of complaints is a factor in deciding on whether to deliver others' email to their inbox or straight to junk (or not accept it at all)
• Set up a system for removing any bounced emails (also used as a measure by the ISPs). As well as monitoring your outbound emails you need to catch everything that comes back to you to process the bounces. It can also help to monitor whether there are delivery problems (e.g. you get a few hundred "delivery deferred" messages from Yahoo).

In the newsletter itself:

• Include a one-click unsubscribe link somewhere in the newsletter. ISP's do check for this in your content.

If you are migrating the newsletter from some Email Service Provider then check that you have downloaded not only the list of emails, but also any other data such as the bounce list, suppression/unsubscribe list and then clean up your email list prior to sending.

While a lot of this isn't server configuration, it's all part of the big picture in what happens when the email leaves your mailserver.

DISK SPACE

check the partitions that will be used if you archive the emails, plus check the log files. If every sent mail will add an entry into a log file, the fill will grow up quickly.

DNS

Morover check that you have an A record + an MX record, which designate the public ip of the server

REVERSE DNS

ideally check the reverse DNS also, some ISP make a reverse dns lookup in order to allow or not the sender.

GREYLISTING

Actually, take care of the gerylisting, it's a recent feature: ISP's block emails for few minutes in order to prevent spamming, non-spammer system are aware of greylisting (ie postifx) and few minutes later the email is send again (spammer don't care about the fact that the mail is blocked or not). If your system does not handle this, then you will have a high failure rate

ERROR FILE

Because you will need to see what goes wrong if an email is not sent

Better DKIM-Signature sign them.

Make sure you have a reverse DNS entry (PTR record) for you mail server.

Cheers