Pserimos, together with the surrounding islets, formed a complex, the "Islands of Kalydnas" as mentioned by Homer.
Pliny calls her Pserema, so we know that her name has been around since ancient times and has been preserved over the centuries.
Already since Antiquity it was one of the municipalities of the Commonwealth of Kos and Kalymnos, a fact known to us from a resolution of the first half of the 3rd century. A.D. In an inscription of the 3rd century, the name Psirimos was written along with a list of lords of Kos, which testifies to the island's dependence on Kos. In recent years, following the fate of the rest of the Dodecanese islands, it submitted to the Ottoman Empire at the beginning of the 16th century. In 1912 it fell into the hands of the Italians, while in 1948 it was incorporated into the Greek state.

The modern settlement coincides with that of antiquity, as remains of the ancient are preserved, i.e. remains of walls, sherds of utilitarian vessels, parts of Hellenistic altars and some scattered architectural members.
Also, remains of early Christian basilicas and architectural elements (pillars, breastplates, capitals, pessicles, pulpit breastplates, altarpiece pillars) are found in the current churches of Taxiarch Michael in Letri, of the Dormition of the Virgin Mary in the settlement in the cemetery, and in the places of Agios Konstantinos and Panagia Grafiotissa.
Between the early Christian monuments and the almost modern ones, no remains of the Byzantine and medieval periods have been found. It is very likely that the island was abandoned and uninhabited during Byzantine times and the Middle Ages.