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I am wondering if with Audio interfaces such as the Scarlett 4i4 is it possible to plug a mic with +48V phantom power in line 1 and plug a guitar into line 2? I mean, if I activate the +48V power, I guess it will be activated for both of the two frontal channels, and I guess the guitar will not work in a 48V line, or it is something automatic that the Audio interface can manage?

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Yes, you can do this. According to focusrite, "48V Phantom power is not sent to any 1/4" jack inputs, these are used for line or instrument inputs." So, plug the microphone into your interface with an XLR cable, and plug the guitar into your interface with a 1/4" instrument cable. It will work.

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The phantom power is only applied across pins on the XLR connections. A guitar plugged in with a 1/4” cable will not have the phantom power voltage on that connection.

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    To emphasise - phantom is never on jacks, only on XLRs. Almost any equipment built in the past 50 years to use XLR is 'aware' of this & will not be damaged if phantom is on but the mic doesn't need it. The plugs/sockets are also designed in such a way that plugging whilst phantom is on is actually better for the equipment than switching it on or off once connected [don't do that if you can help it].
    – Tetsujin
    Oct 21 at 15:35

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