Under the rule of the Ottoman Empire, the village flourished in the 16th century, as it lay on the western trade route between Egypt and Syria. High taxes of different kinds were levied on the busy market. Among other things it traded in cloths, produced in Galilee for international consumption. Public baths and ovens were also taxed. In 1533, Ottoman officials recorded the population as 147 households, and by 1596 (or rather 1548) it grew to 475 Muslim taxpayers (426 households and 49 bachelors) and 96 Jewish taxpayers (95 households and 1 bachelor), making it the sixth most populous locality in Palestine at the time. The villagers paid a fixed tax-rate of 25% on agricultural products, including wheat, barley, olive trees, fruit trees, cotton, goats and beehives, in addition to occasional revenues and a market toll; a total of 56,303 Akçe. At the time, Kafr Kanna was one of a few market villages in the Safad Sanjak and the second largest after the city of Safed. It was also the only locality in the sanjak besides Safed to have a public bathhouse.