Nefopam is a non-opioid, centrally acting, non-steroidal analgesic drug. It is used to treat mild to moderate painful conditions. Although developed about five decades ago, its use has gained resurgence in recent years. This study was designed to investigate the effects of different analgesic doses of nefopam on the liver and kidneys of mice. Forty albino mice were divided into four groups of 10 mice for each group. Group 1, 2 &3 received a daily intraperitoneal injection of Nefopam at 10, 20, and 30 mg/kg doses, respectively. The fourth group (control group) received injections of normal saline. After two weeks of treatment, the animals were weighed and sacrificed, and then blood was collected for liver enzymes analysis and renal function test as well as histological assessment. The results revealed that the bodyweight increase ratio was significantly lower in group 3 (P-value <0.01). All tested liver enzymes i.e., ALT, AST, and ALP levels showed a highly significant (P-value <0.01) change among the tested groups. Although ALT remained within normal limits in the first two groups and normal group, in group 3 (30 mg/kg), its level exceeded the normal value. Liver enzyme changes reflected and supported the histopathological findings in the liver tissue. Group 2 & 3 showed varying degrees of hepatotoxicity, ranging from granulomatous lymphocytic infiltration to micro-vesicular steatosis and apoptotic pictures. Both kidney function test and histopathological examination, on the other hand, illustrated insignificant effect (P-value >0.05) of Nefopam on the kidneys. Nefopam is well tolerable by the liver at low analgesic doses but may have detrimental effects at higher analgesic doses and prolonged duration of intake.