About 7,000 jobs are being cut, and potential replacement positions evaporated last year when President Obama scrapped plans to return astronauts to the moon.
The Space Coast is still reeling from the housing crisis, making it tougher for workers to sell their homes and move to find a job.
"Everything is taking a turn for the worst, it seems like," said Kevin Smith, the local president of the union for space center firefighters, paramedics and workers at emergency landing sites. "What little is out there, everybody is competing for."
Engineer Tony Crisafulli is among those who will be laid off two days after Atlantis returns.
"We're all out here working, knowing that we're losing our jobs in a few days," said Crisafulli, who has been at the space center for nearly 23 years.
Space workers had been looking to the Constellation moon program to cushion the blow from the shuttle program's end. The cancellation of that project eliminated 2,000 jobs.
The Obama administration's space plan has NASA building a new capsule and giant rocket to take astronauts to an asteroid and eventually Mars. It relies on private companies to build their own spacecraft to fly cargo and astronauts to the International Space Station.
The local jobs agency estimates that NASA infuses $1.2 billion into Florida's economy, and that two jobs are lost for each aerospace job that is eliminated.
At the height of the shuttle program, Kennedy Space Center had 17,000 employees who mostly worked for private contractors. After the shuttles retire, there will be a little more than 8,500. They will wrap up the shuttle program and prepare the orbiters for museums, work on unmanned launches and develop and test the new space capsule.
Raymond Steele has been struggling since he lost his job as a logistics engineer for the scrapped moon program and his marriage collapsed. But the 57-year-old is more worried about the future of the Space Coast that he still calls home.
"There is just a huge ripple effect," he said. "It comes down to not just jobs but communities."