The nature of MacDonald's injury has not yet been disclosed.
MacDonald (12-1) has won three of his four UFC bouts, the lone setback coming against highly ranked contender Carlos Condit in June 2010. Despite that loss, MacDonald is regarded as one of UFC's most promising welterweights.
In his two fights this year, MacDonald put on impressive performances. He overpowered Nate Diaz en route to a lopsided unanimous decision at UFC 129 in April, and registered a first-round TKO of Mike Pyle at UFC 133 on Aug. 6.
With MacDonald unable to compete, fellow Canadian Claude Patrick now will face Ebersole on the Dec. 10 card in Toronto.
Patrick (14-1 and undefeated in UFC competition) will be making his fourth appearance inside the Octagon, but Ebersole (48-14-1, one no-contest) represents the stiffest test of Patrick's mixed martial arts career. Ebersole has won two straight since joining UFC and nine in a row overall.
Franklin McNeil covers mixed martial arts and boxing for ESPN.com. Follow him on Twitter at www.twitter.com/Franklin_McNeil