I've had some issues with classes that try to do too much in constructor like creating new http clients and setting headers etc. Removing that part of the code outside of constructor helped in my case. (One method had a lock() somewhere in the internal .NET native code for adding headers to httpclient that went bananas on one server)

@Ryan, do you register instances as singleton? In that case, there's a risk that when some dependency is created, it's created in a faulty state and that faulty state will be used until you restart (or the instance is recreated for some reason). On restart, the singleton instance will be created again and if you're lucky - maybe in the correct state.

I don't think it has anything to do with being registered without a interface, it should work equally good to register just the concrete type.