Cone snail venom contains a diverse mixture of biologically active peptides used for predation and defense purposes, by targeting varies classes of ion channel and receptors at sensitive cells with a high level of affinity and selectivity. Some studies showed that some fractions of scorpion and snake venoms have remarkable neuropharmacological effects on various animal models. However, the studies on cone snail venoms in this field are rare, and accordingly; the current study was designed to evaluate the analgesic, antipyretic, and anti-inflammatory activities of the Conus vexillum venom.Two doses of crude venom (1/10 and 1/5 LD₅₀, 2.42 and 4.84 mg/kg, respectively) were intraperitoneally injected into the experimental animals. In mice, the peripheral and central analgesic effects were examined using acetic acid-induced abdominal writhing and tail immersion test. Brewer's yeast-induced pyrexia in rats was carried out to determine the antipyretic activity of the same doses. Finally, the anti-inflammatory activity was tested using carrageenan-induced paw edema in rats. The results showed that C. vexillum venom produced a significant analgesic activity in acetic acid-induced abdominal constriction response and thermal nociception in mice. Moreover, the venom revealed a significant antipyretic effect on yeast-induced pyrexia. In paw edema, venom showed a significant activity with the highest percentage of inhibition reaching 34.07% and 51.36% on 1/10 and 1/5 LD₅₀ doses, respectively after 5-hour treatment, the latter dose almost equal the effect of the standard drug; diclofenac sodium (56.3%). These results revealed potential analgesic, antipyretic, and anti-inflammatory effects of both C. vexillum venom doses in various animal models.