McDaniels said Moreno, who missed the entire preseason with a pulled right hamstring, would be absent in the Broncos' game Sunday against the Indianapolis Colts.
"I'm telling you every team is dealing with" injuries, McDaniels told The Denver Post. The Colts "have more guys on their injury report than we do. That's why you have a roster full of players."
The newspaper, citing two NFL sources, said Moreno had suffered another hamstring pull, but this time to his left leg.
In Denver's first two regular season games, Moreno has rushed 39 times but for 111 yards -- a 2.8-yard average -- and two touchdowns.
The Broncos seem likely to rotate Correll Buckhalter and newly acquired Laurence Maroney at tailback with Moreno out.