You're talking to someone at a party. He sneezes. You say:
"Bless you!" is the standard response whenever someone sneezes near you. You should say "Bless you!" when you hear someone sneeze.
You can use this expression with people you know, or even with strangers. The word "bless" is usually related to religion, but in this phrase it doesn't really suggest anything religious. It's just something that people say.
A good response to "bless you" is "Thanks" or "Thank you."
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