Herein, two classic animal behavior despair tests-the forced swim test and tail suspension test were used to evaluate the antidepressant-like activity of saringosterol from Sargassum fusiforme in mice. Saringosterol was found to significantly shorten immobility time in the forced swim test and tail suspension test at doses of 10, 20, and 30 mg/kg in mice. The measurement of locomotor activity indicated that saringosterol had no central nervous system-stimulating effects. In addition, it was found that the saringosterol significantly increased noradrenaline, serotonin (5-HT), and the metabolite 5-hydroxyindoleacetic acid in the mouse brain, suggesting that the antidepressant-like activity may be mediated through these neurotransmitters.