The deceased, 48-year-old Forgive Tagbolu and Veronica Agbobli,71, all residents of Abotanso died on their way to the hospital after complaining of stomach upset.
Those on admission are Gracious Tagbolu, Peace Agbobli, Kofi Opare and Agbobli Kofi.
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A member of the family, Kofi Agbobli who confirmed the incident said the victims bought the fish from a market at Donkorkrom.
Hospital medical superintendent, Dr. Zimblim Kasule who confirmed the news said the four are responding to treatment.
Meanwhile, health authorities have recommended their transfer to the police hospital in Accra for autopsy.
He said the autopsy will be conducted to confirm the cause of death.
Pufferfish contain tetrodotoxin, a substance that makes them foul tasting and often lethal to its predators including humans.
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To humans, tetrodotoxin is deadly, up to 1,200 times more poisonous than cyanide.
There is enough toxin in one pufferfish to kill 30 adult humans, and there is no known antidote.
Symptoms of Pufferfish poisoning generally occur 10-45 minutes after eating fish containing the tetrodotoxin.