The Mr. Brightside hitmakers took to the stage at the Manchester Arena and Flowers powered through four hits before leaving the stage to rest his voice.
He tried in vain for 30 minutes to recover but the band decided not to continue with the show.
The group later took to its Facebook.com page to apologise to fans, writing, "Manchester, we started something we couldn't finish and we're so, so sorry. Working on rescheduling tonight and tomorrow's shows. Will let you know new dates Asap."
The rockers have also cancelled a second show in the city on Wednesday (14Nov12).
A representative for the Arena adds, “The two Manchester Arena shows by The Killers on Tuesday 13 & Wednesday 14 November have been postponed.
"Lead singer Brandon Flowers had to take a break early into Tuesday evening’s performance after complaining of a sore throat. Unfortunately, he was unable to continue with the rest of the show.
"Wednesday night’s Manchester show has also been postponed. The band intend to reschedule both Manchester concerts for next year. Confirmation of the new dates is expected within 48 hours."