Background: Cirrhosis is a chronic liver condition characterized by significant morbidity and mortality. Hepatic encephalopathy (HE), a neuropsychiatric complication of cirrhosis, is associated with vitamin D deficiency, which may exacerbate liver dysfunction. Understanding the clinical and laboratory characteristics of cirrhotic patients with and without HE is crucial for improving management strategies. Objective: To evaluate the clinical characteristics of cirrhotic patients and investigate the association between serum 25-hydroxyvitamin D levels and the severity of HE. Methods: This cross-sectional observational study was conducted at Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, from December 2019 to August 2020. A total of 54 cirrhotic patients were divided into two groups: 27 with HE (cases) and 27 without HE (controls). Clinical history, physical examination, and laboratory parameters, including serum 25-hydroxyvitamin D levels, were assessed. Data analysis involved chi-square tests, t-tests, and ANOVA, with a significance level of p < 0.05. Results: The mean age of participants was 50.2 years, with a male predominance (63%). Serum 25-hydroxyvitamin D levels were significantly lower in patients with HE (6.6 ± 2.1 ng/ml) compared to controls (13.6 ± 4.2 ng/ml; p < 0.0001). Vitamin D levels decreased progressively with higher HE grades. Cases exhibited significantly higher serum bilirubin, prothrombin time, INR, Child-Pugh scores, and MELD scores than controls (p < 0.05). Conclusion: Vitamin D deficiency is strongly associated with the severity of HE in cirrhotic patients. Lower vitamin D levels correspond to higher grades of encephalopathy, emphasizing its potential role in HE pathophysiology. Future studies should explore the therapeutic implications of vitamin D supplementation in this population.