Could you make a dump using strace:

strace -s 256 -tt -p <PID of stuck ODBC poller> -o /tmp/ZBX-21409.trace

A few minutes is enough.

ZBX-21409.trace

At the time of this dump, 7 of 10 pollers are "stuck". And none of SQL servers are down and without issues.

I took a couple of samples and have the same info "connection timed out".

Thank you! please show us "lsof -p <PID of the same process like you took strace>".

Sorry, by the time I saw your comment, I had to restart the service because all pollers got "stuck" and I got a lot of false positive alerts. If you need it to be "stuck" we have to wait until it happens again.
Let me know.

Yes, please! Also it would be great if you can share with lsof information about:

zabbix_server -R diaginfo=locks

Anyway, did you try official MSSQL driver from Microsoft?

Ok, I uploaded the 3 files, each containing the information you needed.

Currently I only have 1 "stuck" poller.

ZBX-21409.locks
ZBX-21409.lsof
ZBX-21409-1.trace

It's highly likely that it hangs inside driver library, please try upgrading it or making sure that same library version is used as the one that worked before with 4.0

Also, maybe you can try official MSSQL driver from Microsoft? Looks like the problem in freeTDS implementation.

FreeTDS version is the same when we had 4.0. There is no new versions to upgrade.
I'm trying to use official driver, but it isn't working. Using sqlcmd from the console, I can connect, but at the Zabbix frontend the error is: TCP Provider: Error code 0x2746]|[08001][10054][[unixODBC][Microsoft][ODBC Driver 18 for SQL Server]Client unable to establish connection]. I also tried ODBC Driver 17.
I followed some workaround about an openssl issue (I don't know why it is related, if connection doesn't need TLS). But no luck so far. I'm using Ubuntu 20.04.

Additionally, I did:

sudo lsof -p 221454 -i

Output:

zabbix_se  221454          zabbix   18u     IPv4          498992163      0t0       TCP x.x.x.x:46322->y,y,y,y:42345 (CLOSE_WAIT)

Then I used this source port 46322 as a filter in tcpdump,

17:10:50.776061 IP x.x.x.x.46322 > y,y,y,y.42345: Flags [.], ack 152495331, win 502, options [nop,nop,TS val 2677219822 ecr 1238967986,nop,nop,sack 1 {0:1}], length 0
17:11:20.838964 IP x.x.x.x.46322 > y,y,y,y.42345: Flags [.], ack 1, win 502, options [nop,nop,TS val 2677249885 ecr 1238967986,nop,nop,sack 1 {0:1}], length 0
17:11:50.839017 IP x.x.x.x.46322 > y,y,y,y.42345: Flags [.], ack 1, win 502, options [nop,nop,TS val 2677279885 ecr 1238967986,nop,nop,sack 1 {0:1}], length 0
17:12:20.934753 IP x.x.x.x.46322 > y,y,y,y.42345: Flags [.], ack 1, win 502, options [nop,nop,TS val 2677309981 ecr 1238967986,nop,nop,sack 1 {0:1}], length 0

You can see it's forever trying to connect with the same source port (normally is dynamic), in a 30 seconds interval. I check all .conf files and I did not find any 30 seconds timeout. Zabbix is 4 seconds, Freetds is 10 seconds. And of course, other pollers are connecting to the same server without issues.
Still, my doubt is: why if I restart Zabbix service "systemctl restart zabbix-server" it returns to normal operation?

what mssql version did you test with official driver? Zabbix just pass request to odbc driver, then it trying to connect, Zabbix waiting

Microsoft SQL Server 2016 (SP1-CU15-GDR) (KB4505221) - 13.0.4604.0 (X64)
Standard Edition (64-bit) on Windows Server 2012 R2 Datacenter 6.3 <X64> (Build 9600: ) (Hypervisor)

Please check, maybe some feature is not available: https://docs.microsoft.com/en-us/sql/connect/driver-feature-matrix?view=sql-server-ver16#table2. Do you use AD auth?

No, we don't use AD auth.

could you check this thread: https://stackoverflow.com/questions/57265913/error-tcp-provider-error-code-0x2746-during-the-sql-setup-in-linux-through-te/57343207#57343207

I'm still unable to make it work. I should stick with Freetds driver.