After eight straight wins, Germany need just a point in Belfast on Thursday to be sure of a place at Russia 2018.
However, the world champions have both Werner, 21, and veteran striker Mario Gomez sidelined by injury.
Gomez twisted an ankle last month while Werner is out with neck and spine problems.
The RB Leipzig forward had complained of dizziness in last Wednesday's Champions League game at Besiktas, where the problems first emerged.
“Now is not the time to think about playing, we simply have to make sure that Timo is fit,” said Leipzig's coach Ralph Hasenhüttl after Werner missed Sunday's 2-1 Bundesliga win at Cologne.
Germany's head coach Joachim Löw has said he will not call up replacements.
Löw is likely to start either Moenchengladbach's Lars Stindl, Hoffenheim's Sandro Wagner or Manchester City's Leroy Sane up front against the Irish.
Germany are already without world-class goalkeeper Manuel Neuer, out until January with a fractured foot.
In midfield, Löw is missing Mesut Ozil, Sami Khedira and Mario Goetze, who is still below-par after having only returned in August following seven months off with a metabolic disorder.
Germany expect a tough match in Belfast, where Northern Ireland have yet to concede a goal in their four home qualifiers so far.
The world champions ran out 2-0 winners when the teams met in Hanover last October.
Bayern Munich defender Jerome Boateng is set to make his first appearance for more than a year.
In Neuer's absence, Barcelona's Marc-Andre ter Stegen is set to keep goal.