Regulatory approval is being sought to use praziquantel (PZQ) to treat flukes infecting yellowtail kingfish (YTK), but accurate safety data were not available. We investigated the effect of increased doses or prolonged exposure of orally administered PZQ on YTK by assessing changes in haematological and biochemical characteristics, and mortality. Fish were intubated daily for 3 days with 0, 100, 300 and 500 mg PZQ kg−1 BW day−1 or once daily for 9 days at 0 and 100 mg PZQ kg−1 BW day−1. Blood was taken 24 h after the cessation of treatment. There was no significant difference between any of the haematological or biochemical indices in YTK treated with PZQ and controls, indicating that PZQ is safe for use at 100 mg PZQ kg−1 BW day−1 in YTK and that exposure to high doses or prolonged duration does not have negative effects on the YTK haematological or biochemical parameters we measured.