The Giants placed the five-year veteran on injured reserve Thursday with a herniated cervical disk after waiting more than a month to see if rest would fix his neck.
With Kiwanuka's contract up after this season, it's unknown if the Giants are willing to re-sign a player with a neck problem.
"It's painful for us to go this route with Kiwi, but we've exhausted all of our options," Giants general manager Jerry Reese said. "What's most important is for him to get healthy. We're praying and hopeful that by next fall he will be back at 100 percent and playing for the New York Giants."
Kiwanuka was having an outstanding season, with four sacks in the first three games. He was diagnosed with a cervical disk problem before the Giants played the Chicago Bears early this month and missed the past four games.
"We held out hope as long as we could," Giants coach Tom Coughlin said. "Finally, by consensus, the doctors came to this decision. You have to make the right choice, and the decision was made that he could not play again this season. My concern is for Mathias. He loves the game, he loves to play, he's proven his versatility this year beyond any question."
This is the second major injury for Kiwanuka, the Giants' first-round draft pick in 2006. He broke his left leg in November 2007, the season the Giants beat the previously New England Patriots to win the Super Bowl.
"Like I said before, I felt like, given enough time, I could've made it back this season, but it's the nature of the business," Kiwanuka said. "The Giants had to move on, and I had to be OK with it. Regardless of what happens to me as an individual, I'm definitely still going to work with the Giants' organization throughout the term of my contract. I know this team is going to be successful, so I'm excited to watch it."
Kiwanuka, who said he isn't in pain, hopes to avoid surgery.
"The consensus is that if I take the proper amount of time off, there is a very good chance that it'll heal on its own," he said. "That's what the goal is right now. If it doesn't happen, we'll cross that bridge when we get to it. Regardless of whether or not it requires surgery, I'll still be back by the opening of training camp."
Blackmon was Kiwanuka's roommate during their senior season at Boston College. The two had dinner Wednesday night.
"It's tough, because we were a couple of weeks away from playing together again," Kiwanuka said. "He got his papers from Green Bay, I was excited and heard there was a chance that he might come here, so I've been talking him up around the locker room. Man, he's a great player."
"We expect him to get into the mix quickly on special teams," Reese said. "He has experience and production as a return specialist and cover specialist. He also has played both safety and corner, which gives us some flexibility there as well."
Blackmon played three games last season before suffering a season-ending knee injury Oct. 5 at Minnesota. He was in camp with the Packers this summer, but the sides reached an injury settlement Sept. 5.
Copyright 2010 by The Associated Press