When someone responds to a statement by saying "Of course," does that seem condescending to you?

That or total agreement, depends on the tone!

Not necessarily, no.
I think using “of course!” with the inflection of enthusiastic agreement vs. “of course”, spoken in an arrogant tone is what makes the difference. As always tone and inflection can drastically alter the delivery of many words.

Of course not.

It depends on the tone. If I’m having a pleasant conversation to where I’m agreeing with the person I’ll say that.

I agree, tone of voice matters in this case.

Another vote for “tone of voice.” I’ve heard it used (and used it myself) to indicate that I’m entirely on the speaker’s side, and so would be anyone of sound mind.

Depends on the tone of voice…
“Obviously,” and “Clearly” are usually condescending also.

Not usually, but it can be used that way. I agree that tone is important.

I’d say the majority of times it is not said in a tone that sounds condescending to me, but I do know what you mean and have definitely heard it used that way. But usually it’s, “Hey, wanna get chinese food?” “OF COURSE!”

No.

Of course, I agree.—a smile or nod—
Of course, on the other hand. 2 raised eyebrows
Of course, everybody knows that and aren’t you a dope. a slight sneer + 1 raised eyebrow
You have to infer meaning from facial expressions and voice inflection. And don’t be overly sensitive without reason.

Get here late and all the obvious jokes are taken. Bummer.

However I do not think it is always or even often condescending. In fact, I associate it mostly with servers who are taking my order. Do they have french fried gummy worms? Of course!

Nothing is necessarily anthing, all the time, in all circumstances so I am going with the tone of voice people… but maybe you should go right to the source and ask the horse.