Yes, always, assuming that the state abbreviation is not the end of the sentence.
For example:
No comma needed:
I spent my winter in Detroit, MI.
Unfortunately, I got caught in a snowstorm in Saginaw, Mich.
Comma needed:
The temperature difference between it and Orlando, FL, nearly sent me into shock.
I managed to lose my winter coat in the Knoxville, Tenn., airport while transferring to a different flight.
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