In addition to its well-known effects on bone metabolism, vitamin D is an immunomodulating hormone. Serum vitamin D levels in males 18-25 years were measured at baseline, and HPV antibody titers were measured one month following the third quadrivalent HPV vaccine dose. Vitamin D levels were ≥ 30 ng/ml (normal) in 60 males and <30 ng/ml (low) in 113 males. Reverse cumulative distribution curves and scatter plots showed higher antibody titers with low vitamin D for all vaccine strains (P < 0.05). In linear regression analyses, antibody titers for all HPV strains were significantly higher among those with lower vitamin D levels and among younger participants (P < 0.05). These relationships add to the body of knowledge of the complex role of vitamin D in immunoregulation.