James went down with an ankle injury last week in a preseason game against the Houston Texans. The former Oregon Duck standout did return to practice on Tuesday and seemed to be running healthily.
In addition, fellow half back Brandon Jacobs didn't make the trip to Denver either, as he was held out with a knee injury. This will give backup rushers Rock Cartwright and Anthony Dixon plenty of time on the field against the Broncos.
It appears that Manningham may have experienced the death of a friend of family member. Manningham wrote on his Twitter page, "Lost for words. I just lost a man that knows me better than anyone can imagine have mercy on me!!! Rip Big Daddy"
Randy Moss and Michael Crabtree will get the start at wide receiver.