Magnesium hydroxide nanoparticles (MgOHNPs) have gained commercial interest in the areas of waste remediation and recycling of wastewater for portable use. MgOHNPs is among the least investigated nanoparticle and thus its toxicological effects is yet to be unveiled. Clarias gariepinus were exposed to 62.5, 125, and 250 mg/L suspensions of small size (10 nm) MgOHNPs for 21 days under semi-static conditions. Thereafter, they were sacrificed and alterations in the hematological parameters, and some biochemical indices were examined. The nanoparticle was characterized by UV/Vis spectrophotometry, and Fourier transform infrared spectroscopy (FTIR). The water quality parameters such as chloride ions and dissolved oxygen significantly decreased, while pH, total alkalinity, carbon (IV) oxide, total hardness, and nitrate increased significantly in the exposed media compared to the control medium. The results of this investigation revealed a concentration-dependent increase in the plasma levels of albumin, total protein, magnesium, calcium, chloride, alkaline phosphatase, and acid phosphatase. Whereas, the levels of aspartate aminotransferase, alanine aminotransferase, glucose, total bilirubin, potassium, and creatinine decreased significantly (𝑃 < 0.05). The hematological parameters remained unaltered in the fish at the tested doses.  The results indicated that exposure to MgOHNPs could lead to disturbances in blood biochemistry of C. gariepinus