I had a similar issue when I initially installed Klipper on my Ender 3 S1 (not the plus). It would not connect unless I fully restarted Octoprint whenever I turned on the printer. The change I needed to make was go into settings in Octoprint (though I assume its similar on other front ends), and add the following settings:
Serial Port: /tmp/printer
Baud Rate: 11520

If that is not the case for you, try to add some more details. Do you have the config file correct?