When I've had this issue, I chalked it up to entropy on the system over time. Assuming the config and the ports are all good, then I start with some simple and basic things:
Run splunk stop and then do a kill -9 on the results of: ps -ef | grep -i splunk | grep -v grep | awk '{print $2;}' to stop anything that didn't actually shut down
Restart the actual server thereby purging any zombie processes that might not be needed but are still running from usage over time
When all else fails, reinstall that instance. This can be made easy through proper use of the configuration distribution features
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