Four adult female freshwater teleost fish species; Malapterurus electricus, Synodontis schall, Labeo niloticus, and Lates niloticus (n=7) were collected in both pre-spawning and spawning seasons. The brain was dissected and the cerebellum was separated. The cerebellum was examined histologically by light and transmission electron microscope. cerebellar immunohistochemical stain was performed to investigate follicle-stimulating hormone (FSH) and glial fibrillary acidic protein (GFAP) for the assessment of the level of sex hormones and oxidative stress respectively. Biochemical measurements were executed to measure the brain contents of serotonin, dopamine and fatty acids and the activity of aromatase, Glucose 6 phosphate dehydrogenase (G6PD), Adenosine triphosphate (ATP) and lactate dehydrogenase (LDH). During spawning season, the cerebellar layers appeared fragile except of Malopterurus electricus compared to prespawning season. The cerebellar cortex of the studied fishes with the exception of Malopterurus electricus, is extremely vulnerable to oxidative stress during spawning season. In Synodontis schall and Lates niloticus, many of the cerebellar neurons have lost their myelinated coating. In Lates niloticus, some Purkinje cells exhibited fragmented rough endoplasmic reticulum and some granular cells appeared damaged and pyknotic, while others were surrounded with nerve fibrous sheath. Dense expression of FSH was evidenced during prespawning season, which refers to the increased level of sex hormones if compared with the spawning period. In the studied species, serotonin levels increased during prespawning season while dopamine levels decreased. The spawning period appeared to require higher energy, which was assessed by increasing activity of brain ATPase and G6PD. While LDH activity decreased during spawning that may reflect the absence of some myelinated sheaths. It was concluded that the brain of the studied species exhibited high sensitivity to hormonal alterations during pre-spawning and spawning seasons except for Malapterurus electricus that showed the highest resistance.