Misbah, 40, pulled his hamstring whilst fielding in the second day-night international against New Zealand in Sharjah on Friday and had a scan which revealed he needed to take a three to four week rest.
All-rounder Shahid Afridi leads the side in the remaining matches, with Umar Akmal replacing Misbah in the XI.
New Zealand made three changes with Daniel Vettori, Dean Brownlie and Adam Milne replaced by Martin Giptill, Jimmy Neesham and Nathan McCullum.
The five-match series is currently tied at 1-1 after Pakistan won the first game in Dubai by three wickets while New Zealand won the second, also in Sharjah by four wickets on Friday.
Pakistan: Shahid Afridi (captain), Mohammad Hafeez, Ahmed Shehzad, Asad Shafiq, Haris Sohail, Mohammad Irfan, Sarfraz Ahmed, Sohail Tanvir, Umar Akmal, Wahab Riaz, Younis Khan.
New Zealand: Kane Williamson (captain), Corey Anderson, Martin Guptill, Anton Devcich, Matt Henry, Tom Latham, Mitchell McClenaghan, Nathan McCullum, James Neesham, Luke Ronchi, Ross Taylor. (AFP)