['Vitamin D is an important immune modulator that plays an emerging role in inflammatory and metabolic liver diseases, including infection with hepatitis C virus (HCV). In contrast, the relationship between vitamin D metabolism and chronic hepatitis B (CHB) is less well characterized. Therefore, we quantified 25(OH)D3 serum levels in a cohort of 203 treatment-naïve patients with chronic hepatitis B virus (HBV) infection and tested for their association with clinical parameters of CHB. Of 203 patients, 69 (34%), 95 (47%), and 39 (19%) had severe vitamin D deficiency (25(OH)D3 <10 ng/mL), vitamin D insufficiency (25(OH)D3 ≥10 and <20 ng/mL), or adequate vitamin D serum levels (25(OH)D3 ≥20 ng/mL), respectively. In both uni- and multivariate analyses, HBV DNA viral load (log10 IU/mL) was a strong predictor of low 25(OH)D3 serum levels (P\u2009=\u20090.0007 and P\u2009=\u20090.000048, respectively) and vice versa. Mean 25(OH)D3 serum concentrations in patients with HBV DNA <2,000 versus ≥2,000 IU/mL were 17 versus 11 ng/mL, respectively (P\u2009<\u20090.00001). In addition, hepatitis B early antigen (HBeAg)-positive patients had lower 25(OH)D3 serum levels than HBeAg-negative patients (P\u2009=\u20090.0013). Finally, 25(OH)D3 and HBV DNA serum levels showed inverse seasonal fluctuations.'] Is low vitamin D serum concentration associated with high levels of hepatitis B virus replication in chronically infected patients?