Among 511/818 (62.5%) eligible children, 40.1% were 25(OH)D deficient (median level 22.5 ng/ml (IQR = 16.4, 31.3)). Children with a confirmed (n = 144, 28.2%) or suspected (n = 94, 18.1%) diagnosis of infection on admission did not have lower 25(OH)D levels overall, except for those presenting in severe septic shock (n = 51, median = 19.2 ng/ml, IQR = 12.6, 24.8; P = 0.0008). In the multivariate analysis, older age and nonwhite race were associated with vitamin D deficiency while summer season, vitamin D supplementation and formula intake were strongly protective. Patients with higher pediatric ICU admission day illness severity by PRISM-III score quartiles had lower vitamin D levels (OR = 1.19 per 5 ng/ml decrease in 25(OH)D, 95% CI = 1.10, 1.28, P < 0.0001) after adjusting for risk factors. When septic shock was added to this model, there was no effect on the association between 25(OH)D level and PRISM-III quartile (OR = 1.18 (95% CI = 1.09, 1.27, P < 0.0001)). There was also an inverse association between 25(OH)D level and maximal vasopressor use as measured by the CV-SOFA score in a multinomial regression model (OR = 1.13, 95% CI = 1.01, 1.27, P = 0.03). Including septic shock in the multivariable model did not affect the effect of vitamin D level (OR = 1.16, 95% CI = 1.02, 1.31, P = 0.02)) on CV-SOFA score.