Background: Skeletal muscle cramps (MCs) are observed in around 29–88 % of patients who have liver cirrhosis (LC). They commonly result in sleep disturbance and considerably affect quality of life (QoL). This study aimed to evaluate the validity of measuring serum electrolytes (Na, K, Ca, Mg, and P) and vitamin D among cirrhotic patients who had skeletal muscle cramps. methods: We performed this case-control study on 72 patients with LC who were allocated into 2 groups: group A (case group of LC patients with skeletal MCs) and group B (control group of LC patients without skeletal MCs). Detailed history taking was collected from all patients; they underwent full clinical examination, pelviabdominal ultrasonography (US), and hematological and biochemical investigations, including measurement of serum electrolytes (Na, K, Ca, Mg, and P) and vitamin D. Results: Serum calcium and vitamin D levels were significantly less among group A than in group B (8.17 ± 0.53 mg/dL versus 8.48 ± 0.57 mg/dL; P=0.017 and 8.1ng/mL vs 18.45ng/mL; P < 0.001. Serum calcium (with Confidence interval (CI) of 0.070-0.898 and adjusted odds ratio (AOR) of 0.252) and vitamin D (with CI of 0.648-0.865 and AOR of 0.749) were the only two independent risk factors of muscle cramps. Conclusions: The study findings suggested a substantial relationship between serum calcium and serum vitamin D and MCs in cirrhotic patients. No remarkable relationship was revealed between serum sodium, potassium, magnesium, and phosphorus with MCs in cirrhotic patients.