Background: Sarcopenia and liver cirrhosis are two prevalent worldwide diseases. The current work aims to compare the effect of L-carnitine alone to that combined with Rifaximin on the skeletal muscle of cirrhotic rats. Methods: Forty adult male rats were divided equally into four groups. Group I (Control group), group II (Cirrhotic group) cirrhosis was induced by bile duct ligation for 5 weeks. Group III (Cirrhotic+ L-carnitine), rats were given L-carnitine 100 mg/kg orally daily for 5 weeks from the first day of induction of liver cirrhosis. Group IV (Cirrhotic+ L-carnitine+ Rifaximin) rats were received L-carnitine (100 mg/kg) with Rifaximin (100 mg/kg) orally daily for 5 weeks from the first day of induction of cirrhosis. Skeletal muscle tissue was prepared for H&E staining, immunohistochemical staining for Bax and CD34 and electron microscope examination. Blood samples were collected for serum alanine aminotransferase (ALT) and albumin measurement. Plasma and muscle ammonia, serum levels of lipopolysaccharide (LPS) and IL-6 measurements were also assessed. Results: H&E-stained sections showed disorganized fibers with congested blood vessels in group II while electron photomicrographs showed areas of myofibrillar loss. Some muscle fibers appeared organized and others disorganized in group III. Most of the muscle fibers in group IV appeared nearly normal. Regarding LPS, IL6, ammonia, myostatin and TNF expression, the highest mean values were observed in group II while the least mean values were observed in group IV. Conclusion: Combination of L-carnitine and Rifaximin has a more ameliorative effect on the histological and biochemical changes induced by liver cirrhosis on the skeletal muscle of adult male albino rats.