Desmond switched his uniform number to 20 at the beginning of the 2012 season to honor Frank Robinson. On Opening Day, Desmond started at shortstop and hit leadoff for the Nationals, who played at the Cubs. Desmond was selected for the 2012 All Star Game, his first such selection. However, on Saturday, July 7, it was announced that Desmond was withdrawing from the game due to a sore oblique. The oblique injury persisted, forcing the Nationals to place Desmond on the 15-day disabled list on July 23.