I have an expensive series of http operations. Does proto-repl respect defonce? Can i just defonce the results of my operation, and trust it not to evaluate it anymore?

I can’t imagine protorepl doing anything unexpected there.

ProtoREPL just sends code to the REPL -- the REPL will do the right thing there (as long as you're not refreshing namespaces, but that's still just the REPL doing what it does).