Asthma affects over 8% of the pediatric population in the United States, and Memphis, Tennessee has been labeled an asthma capital. Plasma samples were analyzed for biomarker profiles from 95 children with severe asthma and 47 age-matched, hospitalized nonasthmatic controls at Le Bonheur Children’s Hospital in Memphis, where over 4000 asthmatics are cared for annually. Asthmatics exhibited significantly higher levels of periostin, surfactant protein D, receptor for advanced glycation end products and β-hexosaminidase compared to controls. Children with severe asthma had lower levels of IgG1, IgG2 and IgA, and higher levels of IgE compared to controls, and approximately half of asthmatics exhibited IgG1 levels that were below age-specific norms. Vitamin A levels, measured by the surrogate retinol-binding protein, were insufficient or deficient in most asthmatic children, and correlated positively with IgG1. Which came first, asthma status or low levels of vitamin A and immunoglobulins? It is likely that inflammatory disease and immunosuppressive drugs contributed to a reduction in vitamin A and immunoglobulin levels. However, a nonmutually exclusive hypothesis is that low dietary vitamin A caused reductions in immune function and rendered children vulnerable to respiratory disease and consequent asthma pathogenesis. Continued attention to nutrition in combination with the biomarker profile is recommended to prevent and treat asthma in vulnerable children.