Saying “God bless you” to someone who sneezes is not found in the Bible. However, both the Old and New Testaments provide examples of people blessing others in God’s name. For instance, God told Aaron to bless the Israelites in His name (Numbers 6:24), and David blessed the people “in the name of the Lord of hosts” after celebrating the return of the Ark of the Covenant to Jerusalem (2 Samuel 6:18). In the New Testament, Paul frequently blessed the recipients of his letters (Romans 15:33; 2 Corinthians 13:14; Ephesians 6:23).
Some believe that the custom of blessing someone who sneezes originated as part of a superstition. The Bible warns against participating in superstitious practices (Deuteronomy 18:9-13; Acts 19:18-19), but as long as saying “God bless you” is not meant superstitiously, it’s fine. Another consideration is that believers must never refer to God frivolously (Exodus 20:7). Christians can say “God bless you” as long as we truly mean it.
Sneezes are annoying interruptions that force your eyes closed, usually come in multiples, and tend to go away the moment you grab a Kleenex. But they’re unique in another way, too: They prompt a blessing, even in our secular society.
Blessing someone who sneezes probably started as a first century superstition about sneezing being the body's attempt to get rid of evil spirits. Some believed that the heart stopped when a person sneezed, making him vulnerable to evil spirits. The phrase “God bless you” became a sort of protection or verbal talisman to protect the sneezer.
During the Italian plague in AD 590, people thought sneezing signaled that a person was infected. Legend has it that Pope Gregory I declared that people should respond to a sneeze by saying "God bless you" and then make the sign of the cross over their mouth.
There is nothing wrong or unbiblical with invoking God's blessing on someone who sneezes (and on those who don't!). Believers should show care and concern for others, and saying “God bless you” can be part of that.