Businessman Wesley Deeds is jolted out of his scripted life when he meets Lindsey, a single mother who works on the cleaning crew in his office building.

In Los Angeles, the police put a residential building in quarantine. Meanwhile, the flight attendants of Trans Sky Air, Jenny and Paula, are welcoming the passengers of flight TS Air 318 from Los Angeles to Kansas City with Captain Forrest and Co-Pilot Wilsy. Teacher Henry brings a cage of hamsters to the cabin, but Jenny tells him that it should be transported in the cargo hold. However, one hamster bites the fingertip of the fat passenger Ralph. Soon, Ralph vomits and becomes aggressive, attacking Paula. The male passengers help Jenny and lock Ralph in the bathroom while Captain Forrest requests an emergency landing. When they land in the airport, they find all the gates closed and the Captain heads the plane to an abandoned terminal. Employee Ed helps the crew and passengers to reach the exit, but they find that they are closed. Soon they discover that the place is in quarantine and there is no way out.