Abstract Fipronil sulfone, a major metabolite of the insecticide fipronil, has been found to possess greater toxicity than its parent compound. This study aims to investigate the histopathological effects of acute fipronil sulfone exposure in male mice. The research demonstrated significant tissue damage across several vital organs, including the testis, seminal vesicle, kidney, liver, and brain. Histological examination revealed marked alterations in tissue architecture, such as an increase in interstitial space, degeneration of seminiferous tubules, and neuronal damage. Histomorphometric analysis was performed using ImageJ software to quantify these tissue changes, highlighting the severity of the damage. Specifically, the testis exhibited disruption in spermatogenesis, with altered seminiferous tubules and a significant increase in interstitial space. The seminal vesicle showed signs of metaplasia and epithelial changes. Kidney tissues presented with increased Bowman’s space and degeneration of renal tubules, while the liver exhibited glycogen accumulation, hepatocyte degeneration, and signs of apoptosis. Notably, the brain showed degenerative changes in hippocampal neurons. This is the first study to provide histopathological evidence of the toxic effects of fipronil sulfone on these organs. The results suggest that fipronil sulfone induces significant organ damage through mechanisms such as oxidative stress. Further studies are required to investigate the underlying molecular mechanisms and to assess the long-term risks posed by fipronil sulfone exposure.