Primarily, sleep allows the brain to recover and regenerate. In view of this, central nervous system disorders are the most common effects that result from sleep loss or prolonged periods of wakefulness since the system most benefits from sleep. Therefore, this increases the risk of schizoaffective disorders such as mania and bipolar disorder. This research was therefore designed to investigate the possible anti-manic and anxiolytic effect of minocycline in mice exposed to sleep deprivation. Twenty-four mice were grouped into four of six animals each (n=6) and orally treated with 10 mL/kg distilled water, 25 or 50 mg/kg minocycline. Treatment was scheduled for 7 days and three out of the four groups were subjected to the sleep deprivation protocol which lasted for 3 days. Afterwards, all groups were subjected to behavioural tests to evaluate anxiety-like behaviour. Subsequently, histology of selected brain regions was carried out. Experimental data were analysed using one-way ANOVA with statistical significance of p<0.05. The results obtained suggested that minocycline ameliorated the manic-like behaviour in mice caused by sleep deprivation. This study therefore concluded that minocycline can be classified as an anxiolytic and anti-manic agent in mice exposed to sleep-deprivation.