Many people believed that the soul was located inside the head, so they regarded the sneeze as a sign that the soul was giving them an omen, which some interpreted as a lucky omen, others as unlucky. The Greeks, Romans, and Egyptians considered the sneeze a kind of internal oracle that warned them in times of danger and foretold future good or evil. Sneezing to the right was considered lucky; to the left, unlucky.

An old Flemish belief maintained that a sneeze during conversation proved the truth of a remark. Such a superstition was also prevalent among the Greeks, the Romans, and the Egyptians.

The custom of uttering a benediction, a "God bless you," after the sneeze is universal, and each country has its own particular superstition concerning it. The Romans believed that the sneeze expelled evil spirits; therefore, the act of sneezing was considered an effort on the part of the person to rid his or her system of evil spirits, and those present at the time would say, "Good luck to you."

There is an old legend that before the time of the Old Testament patriarchs, people sneezed only once, and died. But the patriarch Jacob interceded on behalf of humankind and obtained a cessation of this law on the condition that the benediction "God bless you!" follow every sneeze.

In Iceland, according to legend, there was once a dreadful epidemic in which many people died. In a certain household, a brother and sister observed that everyone around them who succumbed to the disease was first seized by a sneezing attack. Therefore, when they themselves sneezed they cried, "God help me!" Because of this prayer they were allowed to live, and they spread the story of the healing benediction to all the inhabitants of the district. The Icelanders have continued the custom of saying, "God help me!" when they themselves sneeze and "God help you!" when others sneeze.

In England during the seventeenth century, it was the custom for all those within earshot of someone who sneezed to remove their hats, bow, and shout, "God bless you!" In nineteenth-century England, someone originated a rhyme regarding the consequences of sneezing on certain days of the week:

Sneeze on Monday, sneeze for danger. Sneeze on Tuesday, kiss a stranger. Sneeze on Wednesday, sneeze for a letter. Sneeze on Thursday, something better. Sneeze on Friday, sneeze for woe. Sneeze on Saturday, a journey to go. Sneeze on Sunday, your safety seek—for Satan will have you for the rest of the week!

Many people believe that the custom of uttering the benediction "God bless you!" after a sneeze dates from the Great Plague that swept London in 1665. Other traditions are firm in stating that the practice began much earlier during the pontificate of Gregory the Great (c. 540–604; pope 590–604). During this period a deadly pestilence raged throughout Italy that proved fatal to those who sneezed. The pope issued prayers to be said against the plague, accompanied by signs of the cross. It was during this era, according to some scholars, that the custom of crying "God bless you!" to persons who sneezed became definitely established.

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