There are actually two systems.
The purely electronic cab sim is located just before the Line-Out/Headphone output, and is triggered by the Voice switch setting to emulate the sound coming out of the speaker (FR or guitar-mode). This system is independent of the speaker, which can be unplugged or turned down with the Master.
There is a more “organic” cab sim system used on the Direct Out on the back which actually uses the speaker response as part of the tone shaping. This is intended as a “mic replacement” and the speaker needs to be playing at a reasonably normal volume to get good results.