The first mention of the early Christian period in Kos is connected to the visit of the disciple Paul which is mentioned in the book of Paul. This was recorded in the minutes of the first Ecumenical Synod of Nice in 325 and was signed by the bishop of Kos Melifron.
The big earthquake in 469AD signaled the change in the structure of architecture from the Roman times to Christian times. However, the next earthquake was very strong in 554AD and destroyed the city of Kos.This made it difficult for the city to get back to its former glory. Life continued along the same lines till the Arabic Invasion in the middle of the 7th century. Until the 7th century Kos remained a member of the Province of the Islanders whose capital Kos - Early Christian Byzantine Periodwas Rhodes. From the middle of the 7th century Kos belonged to the Kibireoton or Aegean or Samos. In the second half of the 11th century we are informed that Nikiforos Melissinos, husband of Evdokia who was the sister of the emperor Alex the first Komninou resided in Kos where he owned a lot of land. At the same time a large number of royal related people came to Kos like Christodoulou who founded the monastery of Theotokou in Old Pyli. Christodoulou exchanged the land in Kos with land in Patmos where he founded the monastery of St John Theologou. From the 11th century till the beginning of the 14th century Kos had many administrative changes up until the occupation by the Knights of Ioannites.

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