Seinfeld will co-headline a December 19 charity stand-up gig with his Comedian co-star Colin Quinn in New York.
The benefit is to be held at NYCB Theatre in Westbury, with all proceeds going to local relief groups.
Seinfeld said of hosting the fundraiser: "I grew up on Long Island, and New York City is home. This is a tough time for this area, and we're just glad to be able to help in the recovery."
Susan Sarandon and Sherri Shepherd have also hosted benefits in recent days to aid relief efforts.
Hurricane Sandy has destroyed infrastructure throughout the East Coast of the US and left more than 100 people dead.