[2]: 47 The first years of his reign were marked by clashes with the faction gathered around the community of Caesarea, whose main representatives were Jeremias III and later Neophytus VI of Constantinople, despite the fact that Paisius II himself was born in this town.
[3] When later Jeremias III had to retire due to health problems, a Patriarch from Nicomedia (Seraphim I of Constantinople) followed and later again one from Caesarea (Neophytus VI) who reigned six years.
The reign of Neophytus VI was ended by a decision of the Grand vizier, who allowed Paisius II to be reinstalled for his second term in August 1740.
Shortly after however a new opponent arose: the Metropolis of Nicomedia and future Patriarch Cyril V of Constantinople, who voiced the complaints against him and was able to depose him on 28 September 1748.
Cyril V however was supported by a large portion of the populace and by the demagogic monk Auxentius, who instigated riots which culminated in a violent assault on the Patriarchate and the seizure of Paisius II himself.