The USA duo is set to miss the team's friendlies in Europe against Scotland and Austria.
Dempsey, the USA captain, strained his right calf in training on Wednesday. Johnson, who just returned to the Hoffenheim lineup after five weeks on the sideline, is still troubled by his right ankle injury, and will return to his club team.
Both players have been key members of Jurgen Klinsmann's squad in 2013. Dempsey has 10 caps and four goals this year, while Johnson has eight caps.
The U.S. faces Scotland on Friday at Hampden Park in Glasgow (3:00 p.m. ET, ESPN2 and UniMas). On Nov. 19, the team travels to face Austria at Ernst-Happel-Stadion in Vienna (2:45 p.m. ET, NBC Sports Network and UniMas).