Giants coach Tom Coughlin said he did not know the extent of Umenyiora's ankle injury immediately after the game.
Team officials declined to specify which ankle. Giants officials initially said Umemyiora was probable to return, but early in the second half he was listed as out for the remainder of the game.
Umenyiora's absence forced Jason Pierre-Paul to take more snaps at the right defensive end spot and thinned the Giants' defensive depth as it unsuccessfully tried to slow down an efficient Saints offense Monday night.
Umenyiora has compiled 22 tackles this season and ranks second on the Giants for sacks with seven, trailing only Pierre-Paul's 10½.
Meanwhile, New York wide receiver Hakeem Nicks left in the third with bruised ribs but returned before the end of the quarter.
Following the game, Nicks said he was fine despite suffering a rib contusion.
Linebacker Mark Herzlich also suffered a sprained ankle, but said X-rays taken came back negative. However, he did not return to the game because there was pain in the ankle and it was sore.
Information from ESPNNewYork.com's Ohm Youngmisuk and The Associated Press was used in this report.