The charity said tests confirmed all of the cats near Victor Avenue, in Melton Mowbray, Leicestershire, had ingested the toxic substance.
In the most recent case, seven-month-old Meereen died on Monday.
An RSPCA spokesman said it was unclear whether the poisonings were accidental or deliberate.
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Three other cats in the area have died in the last seven days, while another cat died two weeks ago.
Meereen's "devastated" owner, Adria Pearce, said the cat came home on Friday evening and "seemed to be shivering a little".
"I haven't been able to stop crying since she died," she said.
"We found her behind the sofa, where she was foaming from the mouth and trying to be sick."
Meereen was taken to the vets - where it was confirmed she had consumed antifreeze - and died three days later.
RSPCA inspector, Andy Bostock, is appealing for everyone in the area to ensure pesticides and chemicals were stored safely.
"We are very concerned," he said.
"It is the time of year where people use antifreeze in their cars, so if you do, please make sure there are no leaks and any spills are cleaned up properly."
Five cats have died from antifreeze poisoning on or near the same street in the space of two weeks, the RSPCA has said.