A three-month course of the supplement appeared to be as effective as drugs, cutting the rate of psychotic illness like schizophrenia by a quarter.
The researchers believe it is the omega-3 in fish oil - already hailed for promoting healthy hearts - that has beneficial effects in the brain.
A "natural" remedy would be welcomed, Archives of General Psychiatry says.
"The finding that treatment with a natural substance may prevent, or at least delay, the onset of psychotic disorder gives hope that there may be alternatives to antipsychotic drugs," the study authors said.
Antipsychotic drugs are potent and can have serious side effects, which puts some people off taking them.
Fish oil supplements, on the other hand, are generally well tolerated and easy to take, say the scientists.
The international team from Austria, Australia and Switzerland tested the treatment in 81 people deemed to be at particularly high risk of developing psychosis.
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