It would depend on what you wanted to do. If you wanted your operating system sound to go through the UR, you can do that (or not). You would set it as the input/output for Cubase. Yes, you would connect your speakers to the outputs from the UR22. When the UR22 is selected as the ASIO driver for Cubase, all of Cubase’s input and output sound would function through the UR22. I hope this information helps.