Manning was listed as going through a limited practice because of what coach Tom Coughlin called "a stomach bug."
"Hopefully it is just a 24-hour deal and he will feel better tomorrow," Coughlin said.
Manning remained at the practice facility despite not being able to finish practice.
Backup quarterback David Carr estimated that he took 75 percent of the snaps with Manning ill. Still, the Giants were not worried about their quarterback or whether illness would affect his preparation for Sunday's NFC Championship Game against San Francisco.
"I didn't really notice he was sick when we were in the meetings this morning," Carr said. "That's a good sign. He was in there plugging away and he charged through it for a couple hours this morning and then we went out to practice, and I guess he wasn't feeling well."
Manning is the Giants' iron man. He owns the longest consecutive games started streak by an active quarterback with 119 straight regular-season starts, third all-time behind Brett Favre and Peyton Manning.
So it's no wonder why his teammates weren't worried at all.
"No man, it's Eli Manning," defensive end Dave Tollefson said. "You kidding me? They probably got some type of special virus killer that only Eli Manning can use, or something like that. I'd be sick for two weeks. He'll be good tomorrow."
The Giants are at their healthiest state of the season since the opening of training camp. The only player who did not practice on Wednesday was running back Ahmad Bradshaw, who typically takes Wednesdays and Thursdays off to rest his injured foot as part of his routine.
Linebacker Mark Herzlich (ankle) returned to a limited practice after missing seven straight games.
After Manning had to run out of practice, tight end Jake Ballard said "it was a little weird" since Manning is always a fixture at practice.
"It was a little weird but I knew he was hurting bad because he's not the type of guy to say anything and he didn't say anything, he just sneaked off to the bathroom when he needed to," Ballard said. "You could see he was feeling bad. I told one of these guys I couldn't imagine going through practice with the flu and he has to think about so many things before the snap, during the snap. I hope he gets better, but I can't imagine what he's going through."
The Giants need Manning at his best against the Niners. He is in the midst of the finest season of his eight-year career, throwing for a career-high 4,933 yards, 29 touchdowns and 16 interceptions. He also has engineered six game-winning drives this season when the Giants were either trailing or tied in the fourth quarter.
So far in the playoffs, Manning has passed for three touchdowns in each of the Giants' wins over the Falcons and Packers.
Manning spends hours every week studying his opponent and preparing for games. But the Giants weren't worried about this illness affecting his preparation.
"If he didn't have the kind of the red belt mastery of the offense then yeah, maybe, but he does," Carr said. "It's not something that is going to affect him. I think the biggest thing would be the players, the rest of the guys, so what I tried to do is go right in and do exactly what he would do and just try keep the consistency so their practice on Wednesday was as normal as possible, and I think that it was."
Carr, who was the Niners' backup quarterback last season, said he also played the role of Alex Smith for the defense as well.
"I did most of it," Carr said of taking first-team reps. "He left fairly early. I did most of the reps for both sides so I was Alex and trying to impersonate Eli also. Got a good sweat today."
Even though Manning was ill, the Giants weren't sweating it out. Manning knows the Giants offense as well as the coaching staff. And it will take a lot more than a stomach bug to keep Manning off his game.
"If there's one guy who can miss a Wednesday practice mentally I think it's No. 10," Giants guard Chris Snee said. "I'm pretty sure he was in here Monday and Tuesday and has the whole game plan down."
Tuck said, "He'll be ready. I'm not worried."
Ohm Youngmisuk covers the Giants for ESPNNewYork.com.