Families are needed to take in dozens of cats and rabbits before their rescue centre home is sold.
Debbie Campain has been running Cat Rescue at her bungalow in Peacehaven for five years.
But since splitting with her partner two years ago she has struggled to pay the mortgage.
A £30,000 rescue package offered by an anonymous donor in January fell through when Ms Campain realised she still could not afford the centre's running costs of around £2,500 per month.
Now she has stopped taking in new admissions and is looking for suitable homes for 45 cats, four rabbits and two lizards before the house is sold.
She said: "I'm afraid there's no way out of it. The house is on the market now so there's no knowing how long we have got to rehome the animals. It could be a week or it could be several months.
"I just think it's better to do it this way than to wait until the house is repossessed and I have no way of controlling where the animals end up."
Ms Campain started working for the centre eight years ago as a manager. Following the death of founder Irene Hubbard five years ago, she moved the centre to her house in Fairlight Avenue.
She works 15 or 16 hours every day, seven days a week, taking in around 800 cats, rabbits and guinea pigs every year.
She said: "Just because we're closing doesn't mean we'll let anybody take the animals. We still won't let a family with children take on a nervous cat."
Sara Harris, 31, from Brighton, is one of five volunteers to join in February following an appeal in The Argus. She said: "I'm so sad it's closing. Debbie does some really interesting work here, helping nervous animals."
Anyone interested in taking on an animal should call Ms Campain on 01273 580464
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