Yes. I even changed the battery in a different room from where the box's power cord was. 
I actually saw a technician change a CMOS battery on a live box once and get away with it, but that was in my music synthesizer, not a computer, even though the two devices have a lot in common. In the synthesizer (Kurzweill PC2-R), changing the battery loses a whole bunch of programming that accommodates the box to my MIDI controller (Alternate Mode’s malletKAT PRO). Then all that programming has to be downloaded again together with the voice modifications I’ve made, otherwise the controller can’t talk to the synthesizer and vice versa. (Who designs a system like that? 
Kurzweill does. 
) She got away with it and we didn’t have to download the interface programming, which BTW can only be done from an Apple iMAC, not any PC. Needless to say, every five years or so when the battery is close to done, I box up my synthesizer and send it back to Alternate Mode to get the battery changed.
