General life history theory suggests a trade-off between somatic maintenance and reproduction. However, in the honey bee, and other social insects, reproduction increases lifespan. The mechanisms for this positive relation between antagonistic demands are unclear but may be related to vitellogenin (Vg), a reproductive protein that has adopted other important survival functions, such as oxidative stress resistance and immunity. To study the role of Vg in survival functions, the susceptibility of reproductive and non-reproductive honey bee workers to Israeli Acute Paralysis Virus (IAPV) and pesticide-related oxidative stress was compared. Workers in the absence of a queen exhibited more active ovaries than workers in the presence of a queen at older (25d) but not younger (15d) ages. Survival measures of paraquant stress and IAPV infections, complemented with an assessment of gene expression patterns, indicated not only the predicted changes in survival and Vg titers but also correlated alterations in the differential expression of other functional domains: Toll-6 and Argonaute-2. These results support the relevance of non-reproductive functions of Vg in worker bee defense against stressors, demonstrating that social manipulations can alter worker physiology and improve resistance to viral and pesticide stressors of queenless workers. Data from this study has not only interesting implications for honey bee immunity and health but also understanding honey bee caste differences.