Andrew Balbirnie and Stuart Thompson have been ruled out of the tournament.
Batsman Balbirnie failed a late fitness test having sustained a glute strain, while all-rounder Thompson suffered an ankle injury during training on Friday.
The event technical committee has approved Stuart Poynter and Lorcan Tucker as replacements for the duo.
"It's unfortunate for both players who were keen to re-establish themselves in the squad having missed most of the 2016 season," said a Cricket Ireland spokesperson.
"Stuart Poynter and Lorcan Tucker are both excellent replacements who I'm sure will acquit themselves well given the opportunity."
Tucker, 20, made his debut last season against Hong Kong, while 26 year-old Poynter has played 10 T20 internationals for Ireland.
Ireland have been drawn in Group A of the eight-team tournament, against hosts UAE, Afghanistan and Namibia.
Ireland's opening match with Afghanistan at the Sheikh Zayed Stadium gets under way at 15:00 GMT.
Ireland have been dealt a double injury blow ahead of their opening Desert T20 Challenge game with Afghanistan in Abu Dhabi on Saturday.